insightVol. XIX No. 3 NOVEMBER 2001

Scientific Journal ofMEDICAL & VISION RESEARCH FOUNDATIONS

18, COLLEGE ROAD, CHENNAI - 600 006, INDIA

Editorial

Perspective — Vascular Tumors of the Retina — Mahesh Shanmugam

Ocular surface, anterior segment and adnexal disorders in AcquiredImmunodeficiency syndrome - Analysis of 45 patients — Iyer GeethaKrishnan, Kannan M. Narayana, Jyotirmay Biswas, Amala E George andRajesh Fogla

Familial band-shaped spheroidal degeneration of the cornea, report of twocases — Geetha K Iyer, Rajesh Fogla & Jyotirmay Biswas

Indocyanine green angiogram in tubercular choroiditis - Case Report— Rupesh V. Agrawal, Dipankar Das, Jyotirmay Biswas, K. Jagannath andH. N. Madhavan

Transpupillary Thermotherapy for Choroidal Melanoma in Asian IndianPopulation — Mahesh. P. Shanmugam and Rajiv Raman

Degraded stereopsis as a presenting sign of Convergence Insufficiency— S.Jayarajini and Shrikant R Bharadwaj

Last Page — Databases and free softwares on the Net for DNA analyses —Vedam Lakshmi Ramprasad, Pradeep George Paul, Sarangapani Sripriya andGovindasamy Kumaramanickavel

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Study of tumors is a fascinatingsubject. Why do tumors occur? Why someare locally destructive while others are lifethreatening? What is that little unknownchemical sequence which is lost, leading tothe occurrence of multisystem tumors inphakomatosis? These questions may beanswered in the future with the mapping ofthe human genome and further advancesin genetics. However, for now we have to besatisfied with rather inefficient methods ofcure than prevention in the management oftumors. Vascular tumors of the retina varyfrom the rather innocuous curiosity, thecavernous hemangioma of the retina to thepotentially blinding capillary hemangioma.

EDITORIAL

Of course, the associated systemic featuresmay be life threatening. The "Perspective"of this issue deals with vascular tumors ofthe retina. In addition, a short case seriesof Indian patients with uveal melanomatreated with transpupillary thermotherapyis presented as an article.

This issue of Insight also contains articlesabout the use of ICG in posterior uveitis, shortcase report on familial climatic dropletkeratopathy, anterior segment disease in AIDSpatients, databases on the web for DNAanalysis and a case report on convergenceinsufficiency affecting the surgical capabilitiesof an ophthalmic surgeon.

Dr. Mahesh P ShanmugamEditor

SIR RATAN TATA FELLOWSHIPTRAINING IN CATARACT SURGERY

(Basic & Advanced)Offered at

SANKARA NETHRALAYAWith Stipend and Accommodation

Holders of Postgraduate Diploma or Degree in Ophthalmology may apply in ownhand enclosing a detailed Bio-data with no objection certificate from the employer(if employed) to undergo training at Sankara Nethralaya.

Fellowship programme of 3 months duration is offered four times a year commencingevery 1st January, 1st April, 1st July and 1st October.

For the 1st January 2002 programme, apply before 7th December 2001.

For further details contact:The Academic Officer

Medical Research Foundation,18, College Road, Chennai 600 006

Fax: 91-44-8254180 e-mail: mrf@sankaranethralaya.org(USE FAX/E-MAIL/SPEED POST FOR CORRESPONDENCE)

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Perspective:

Vascular Tumors of the RetinaMahesh Shanmugam

Vascular tumours of the retina includethe following:

a. Capillary Hemangioma of the retina

b. Cavernous Hemangioma of the retina

c. Racemose Hemangioma

d. Vasoproliferative tumor of the retina

Capillary Hemangioma of the retinaCapillary hemangioma of the retina may

occur as a phakomatosis with central nervoussystem and multiorgan tumors when it iscalled von Hippel Lindau syndrome. 1 It mayoccur without systemic disease as well. It isgenetically transmitted as an autosomaldominant mode with incomplete penetranceand variable expressivity. Von Hippel Lindausyndrome is linked to a defect in short arm ofchromosome 3 (3p 25-26).2

Clinical findings3

The ocular lesions are usually diagnosedbetween 10 – 30 years of age. The earlyangioma appears as a yellow spot between afeeding arteriole and a draining venule. Asthe angioma increases in size, the supplyingvessels increase in diameter and becometortuous. Visual acuity decreases due toexudation or secondary retinal detachmentinvolving the macula. An appearance of dilatedpair of vessels in the posterior pole withmacular exudates should prompt one toexamine the periphery for a capillary angioma.Multiple or bilateral angiomas indicate thepresence of von Hippel Lindau tumor andscreening for central nervous system orsystemic disease should be done. Theexudation in the macular region may be dueto a steal phenomenon or a subretinalmigration.

Some authors believe that two forms ofdisease exist – the exudative form and thevitreoretinal form.3 In the vitreoretinal form,epimacular membranes form which causemacular traction detachment and decreasedvision. Traction on the angiomas can lead to“free floating” angiomas in the vitreous,vitreous hemorrhage and a combined tractionrhegmatogenous retinal detachment can alsooccur.

Angioma of the optic nerve head mayoccur. This differs from the retinal angiomain that no feeder arteriole or a draining venuleis seen. The orange red lesion is ill defined,involves an eccentric part of the optic discwith exudation involving the peripapillaryregion and simulates papilledema.

Without treatment, most eyes progressto total retinal detachment, neovascularglaucoma and a painful blind eye.

Differential DiagnosisThe retinal angioma may be mistaken for

Coat’s disease (no paired dilated vessels incoat’s disease), racemose angioma (no tumorbetween the arteriole and venule in racemoseangioma), intraretinal macroaneurysm (occursalong a arteriole without a draining venule),retinal cavernous hemangioma (no feedervessels; multiple sac like aneurysmaldilatations), familial exudative vitreo-retinopathy, and nematode endophthalmitis.

The disc angioma may simulatepapilledema, optic neuritis, peripapillarychoroidal neovascular membrane and opticdisc granuloma.

Pathology4

The lesions are made of a proliferationof capillaries that usually replace full

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thickness retina with benign proliferation ofendothelial cells and pericytes.

Diagnosis

The diagnosis can be made most oftenon indirect ophthalmoscopy with the classicpicture of an orange tumor with a feedingarteriole, draining venule associated withmacular exudates. A fundus fluoresceinangiogram may however be necessary todelineate early lesions that are not visible onclinical examination. These lesions fill earlyphases of the angiogram and leak profuselylater. The paired vessels are well delineatedas well.

Treatment

Early treatment of retinal capillaryangiomas leads to better visual results. 5,6

Early stages of the angiomas without retinaldetachment are treated with laser photo-coagulation. It is preferable to use green,yellow or blue green wavelength to treat theselesions, as red or infrared lasers may not beabsorbed well. Lesions < 2 mm are treatedwith direct photocoagulation. For lesions 3-5mm, it is preferable to try occlusion of thefeeder vessels – the arteriole in the firstsession and the venule later. The angioma assuch can be treated in subsequent sessions.Hemorrhage from the tumor and increase insecondary retinal detachment may occur ascomplications.

For tumors larger than 5 mm, it ispreferable to use triple freeze thawcryotherapy. A conjunctival incision is usuallynecessary to treat posteriorly placed tumors,while anterior tumors can be treated withoutthe same. Postoperative increase in theexudative detachment is commonly seen,which settles with time. Hemorrhage from thetumor may also occur.

If the tumors are associated with abullous retinal detachment, drainage of thefluid, cryotherapy and scleral buckling maybe necessary. Advanced vitreoretinal form ofthe disease may need vitrectomy to relievetractional or rhegmatogenous retinal

detachment. 7,8 Some authors have triedinternal (vitreoretinal route) or external(transscleral route) resection of single largetumors. Eyes with advanced disease thatneeds surgical intervention usually have apoor visual prognosis.

Transpupillary thermotherapy, plaqueBrachytherapy, proton beam irradiation,external beam radiation therapy have beenemployed in the management of retinal anddisc angiomas. 7,9,10

Systemic features1 1

In contrast to most phakomatosis, vonHippel Lindau syndrome does not have majorcutaneous features. Angiomas, nevi, or café’au lair spots may occasionally be seen.

Cerebellar hemangioblastomas is theclassic central nervous system lesion of vonHippel Lindau syndrome. It usually causescerebellar symptoms in the 4 th decade of lifeand can be imaged on a CT scan. Treatmentis in the form of surgical resection if possible.

Unilateral or bilateral phaeochromo-cytomas, cysts of the kidney, pancreas,epididymis and renal cell carcinomas mayoccur in these patients. It is thus importantto follow up patients of von Hippel Lindausyndrome with periodic neurological andsystemic evaluation.

Cavernous Hemangioma of the retina

Cavernous hemangioma of the retina isalso recognized as a phakomatosis withinvolvement of the retina, skin and the centralnervous system. It appears to have anautosomal dominant mode of inheritance.

Ocular features3

The ocular involvement is usuallyasymptomatic if situated in the periphery ormay cause loss of vision if involving themacula. One patient with a superonasalcavernous angioma has been noted to haveassociated cone dysfunction. 12 The lesionappears as a cluster of dark red saccules withassociated fibroglial proliferation. No feederarteriole or draining venule is usually seen

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though some authors have noted twin vesselsto be associated with this tumor.13 The lesionis non-progressive or may enlarge minimallyover time. The tumor may rarely causevitreous hemorrhage but do not causeexudation. The differential diagnosis of thislesion includes those listed for capillaryhemangioma of the retina.

The lesion consists of endothelial linedvenous aneurysms interconnected by narrowchannels. Associated cystic degeneration ofthe retina may occur.

The diagnosis is evident on fundusexamination but the fundus fluoresceinangiogram is quite characteristic. Theselesions have a slow blood flow which leads tothe separation of the plasma from the bloodcells, which settle down within the saccule.Fluorescein enters the saccule slowly and fillsthe supernatant plasma, enhancing the fluidlevel, creating a “fluorescein cap”.

No treatment is required for this lesion.If vitreous hemorrhage occurs, cryotherapy,photocoagulation, low energy plaque may beused to treat these tumors. 3

Similar lesions involving the centralnervous system may lead to seizures and otherneurological symptoms. Hepatic cavernousangiomas may also occur. 14 Cutaneousangiomas may involve the back or the neck.

Racemose Hemangioma

Racemose hemangioma is more of avascular malformation than a tumor and ifassociated with systemic disease, is called theWyburn Mason syndrome. No definitehereditary pattern has been noted.

Arteriovenous communications inWyburn Mason syndrome have been classifiedin to 3 types.15 In the first type, an abnormalcapillary plexus is interposed between thearteriole and the venule. These lesions do notcause symptoms and are not usuallyassociated with cerebral involvement. In type2 no capillary bed is found and directarteriovenous communication exists and thepatients experience few visual symptoms.

Associated cerebral vascular malformationmay be found. Group 3 patients have morecomplex and extensive arteriovenousmalformation with visual loss and increasedrisk of cerebral disease. One or more dilatedarterioles emanate from the disc, travel for avariable distance in the retina, formarteriovenous communication and return tothe disc. No associated exudation or retinaldetachment is found.

The clinical appearance is characteristicand a fluorescein angiogram may show rapidfilling of the arteriovenous communicationwithout dye leakage.

Most lesions are stationary and do notneed treatment. However, the visual prognosisis poor. Spontaneous intracranialhemorrhages may lead to neurologicsymptoms. Bones of the skull, maxilla, andmandible may be involved, causing massivebleeding during dental extraction. 3 Orbitalvascular malformations may cause proptosis.

Vasoproliferative tumor of the retina

These solitary tumors commonly involvethe inferotemporal of inferior quadrants of theretina. They may occur without anyantecedent cause, but are may associated withprior uveitis, retinitis pigmentosa, Coat’sdisease and familial exudative vitreo-retinopathy and toxoplasma scars.16,17 Theyappear as solitary mass lesions with minimallydilated feeder vessels, associated withintraretinal and subretinal exudation andhemorrhage, secondary retinal detachment,premacular fibrosis, tractional retinaldetachment, RPE hyperplasia, macular edemaand vitreous hemorrhage. Some patients mayhave multiple or diffuse tumors. Thepathogenesis of these lesions is unclear.

Fluorescein angiography shows earlyfilling and late leakage and dilated feedervessels. If progressive exudation causes lossof vision, cryotherapy, photocoagulation,plaque brachytherapy may be necessary. 16,17

Epiretinal proliferation may need vitreoussurgery.

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Reference

1. Wing GL, Weiter JJ, Kelly, PJ et al. vonHippel-Lindau disease. Angiomatosis of theretina and central nervous system.Ophthalmology 1981,88:1311-14.

2. Kreusel KM, Bornfeld N, Bender BU et al.Retinal capillary angioma. Clinical andmolecular genetic studies. Ophthalmologe1999, 96:71-6.

3. Shields JA, Shields CL: A textbook andatlas. Shields JA, Shields CL (eds):Philadelphia, WB Saunders Co, 1992.

4. Nicholson DH, Green WR, Kenyon KR.Light and electron microscopic study ofearly lesions in angiomatosis retinae. AmJ Ophthalmol 1976, 82:193-204.

5. Schmidt D, Natt E, Neumann HP. Long-term results of laser treatment for retinalangiomatosis in von Hippel-Lindau disease.Eur J Med Res 2000, 28:47-58.

6. Lommatzsch A, Wessing A. Retinalangiomatosis Long-term follow-up.Ophthalmologe 1996,93:158-62.

7. Palmer JD, Gragoudas ES. Advances intreatment of retinal angiomas. IntOphthalmol Clin 1997, 37:159-70.

8. McDonald HR, Schatz H, Johnson RN etal. Vitrectomy in eyes with peripheralretinal angioma associated with tractionmacular detachment. Ophthalmology 1996,103:329-35;discussion 334-5.

9. Parmar DN, Mireskandari K, McHugh D.Transpupillary thermotherapy for retinalcapillary hemangioma in von Hippel-Lindaudisease. Ophthalmic Surg Lasers 2000,31:334-6.

10. Garcia-Arumi J, Sararols LH, Cavero L,Escalada F, Corcostegui BF. Therapeuticoptions for capillary papillaryhemangiomas. Ophthalmology 2000,107:48-54.

11. Hardwig P, Robertson DM. Von Hippel-Lindau disease: A familial, often lethal,multi-system phakomatosis. Ophthalmology1984, 91:263-70.

12. Gunduz K, Ozbayrak N, Okka M, OkudanS, Zengin N. Cavernous hemangioma withcone dysfunction. Ophthalmologica 1996,210:367-71.

13. Bottoni F, Canevini MP, Canger R, OrzalesiN. Twin vessels in familial retinalcavernous hemangioma. Am J Ophthalmol1990, 15:285-9.

14. Drigo P, Mammi I, Battistella P A, RicchieriG et al. Familial cerebral, hepatic, andretinal cavernous angiomas: a newsyndrome. Childs Nerv Syst 1994, 10:205-9.

15. Archer DB, Deutman A, Ernest JT et al.Arteriovenous communications of theretina. Am J Ophthalmol 1973, 75:224-241.

16. Shields CL, Shields JA, Barrett J, De PotterP. Vasoproliferative tumors of the ocularfundus. Classification and clinicalmanifestations in 103 patients. ArchOphthalmol 1995, 113:615-23

17. Heimann H, Bornfeld N, Vij O et al.Vasoproliferative tumours of the retina. BrJ Ophthalmol 2000, 84:1162-9

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Introduction:

AIDS is a potentially lethal, multisystemdisorder caused by a retrovirus, the humanimmunodeficiency virus (HIV). Ocular lesionsin AIDS are varied and affect almost allstructures of the eye. Patients can haveophthalmic complications during the earlyphase of AIDS and ophthalmic manifestationof the disease can be the initial manifestationof the underlying systemic HIV infection. Anophthalmologist thereby can be the firstclinician to diagnose or suspect HIV infectionand its associated opportunistic infections.

When the nature and consequence ofinfection with HIV was first recognised it mighthave been predicted that the ocular surfacewould be a likely sight of opportunisticinfection. The fact that it is not often the caseis of considerable interest. Less attention hasbeen directed towards external disease andanterior segment disorders, yet they too maycause severe morbidity and may providediagnostic clues in persons at risk for AIDS.Since the original description of ocularinvolvement in AIDS by Holland and coworkersin 1982,1 a number of clinic based surveyshave been reported from different parts of theworld. 2-5

In India the percentage of AIDS patientsis on rise and so are the ophthalmicmanifestations of these patients. Since thefirst description of first two cases by Biswaset al of ocular lesions in AIDS, 6 there havebeen several reports of ocular lesions in AIDSfrom different parts of India. According to theUNAIDS’ (United Nations AIDS Control

Program) current statistics till June 2000, outof a population of 997 million with a sexuallyactive population of 509 million (15-49yrs) theestimated number of people living with AIDSis 3.7million. Ocular lesions can occur in ashigh as 70% of the patients with AIDS. 1-5

Ocular lesions mainly involve theposterior segment that is the retina andchoroid, however, the anterior segment, ocularadnexa and the ocular surface can also beaffected and can be one of the initial mode ofpresentation. We evaluated the ocular lesionsin HIV positive patients examined at andreferred to our institute our institute andanalysed the anterior segment manifestationsin these patients.

Materials and Methods:

All HIV infected patients who presentedor were referred to our hospital between June1995 to June 2001 were evaluated. A detailedhistory with complete ophthalmic examination,which included visual acuity, external eyeexamination, ocular motility, pupillaryreflexes, anterior segment examination by slitlamp biomicroscopy and dilated fundusexamination with scleral depression was donewith indirect ophthalmoscopy.

Systemic evaluation of these patients wasdone in an AIDS care and research centre inthe city. HIV seropositivity was establishedby Enzyme Linked Immuno Sorbent Assay(ELISA) for HIV1 and HIV 2 and confirmed bywestern blot method. External slit lamp andfundus photograph with the abnormal findingswas documented. Relevant laboratory and

Ocular surface, anterior segment andadnexal disorders in AcquiredImmunodeficiency syndrome -Analysis of 45 patientsIyer Geetha Krishnan, Kannan M. Narayana, Jyotirmay Biswas, Amala E George and Rajesh Fogla

88

radiological examination were carried out inall patients and the information was recordedin a precoded proforma. CD4 and CD8lymphocyte tests were done when indicated.

Results:

Out of the 370 HIV positive patients,examined at our institute in between June1995 to June 2001, 150 (40.54%) patientshad ophthalmic manifestations. CMV retinitsand cotton wool spots were the mostfrequently encountered lesions in thesepatients. Besides that other lesions in theposterior segment were HIV retinopathy, focalchorioretinitis, endophthalmitis, optic atrophy,frosted branch angiitis and vitreoushaemorrhage. Thirty percent (45) of thesepatients were noted to have anterior segmentmanifestions. These were in the form ofblepharitis and meibomitis (13.33%), herpeszoster ophthalmicus (6.66%) (Fig.1),molluscum contagiosum (4.44%) (Fig.2),conjunctival microvasculopathy (2.22%),conjunctival squamous cell carcinoma (2.22%)(Fig.3), nodular scleritis (2.22%), kerato-conjunctivitis sicca with Stevens Johnsonsyndrome (2.22%), corneal opacity (2.22%),healed viral keratitis (2.22%), corneal abscess(2.22%), anterior uveitis (57.78%) andsecondary cataract (2.22%).

Out of the five patients with blepharitisthree were treated with the regular line oftreatment comprising of lid hygiene andantibiotic ointment on the lid margin. One

patient presented with an ulcerative lesionover the medial one third of the eyelid whichrevealed staphylococcus aureus on culture oflid scraping material and was given a courseof oral doxycycline 100 mg daily for two weekswith topical eye ointment besides lid hygiene.Scarring at the lid margin occurred after sixweeks followed four months later bycytomegalovirus retinitis in the same eye,which regressed with intravenous ganciclovir.However the patient died of multiple systemicinfections after a year. The fifth patientrevealed extensive blepharitis with multiplepus points on the upper eyelids in both eyesand was treated with the same therapy asmentioned above. One patient had severemeibomitis and was advised regarding lidhygiene besides regular follow up.

Both the patients with molluscumcontagiosum had extensive lesions on the skinover the eyelids and over the periorbital skinaround and were referred to a dermatologistfor further evaluation and management.

Three patients with herpes zosterophthalmicus had skin lesions at differentstages and two of the patients had associatedanterior uveitis as well. The other patient hadacute retinal necrosis as well and hadundergone cataract surgery in the same eyeone year back. Two of the patients weretreated with oral acyclovir and the patientwith acute retinal necrosis was treated withintravenous acyclovir.

Fig.1 - Herpes Zoster Ophthalmicus

Active Healed

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One patient had a corneal abscessinvolving the whole of the cornea withevidence of early panophthalmitis andtherefore evisceration was done on anemergency basis in this patient. Subsequentlaboratory investigation revealed it to be offungal origin and the organism was detectedto be penicillium.

A conjunctival papillomatous growth withsurface keratinization with prominent feedervessels was noted on the lateral bulbarconjunctiva in one patient and was clinicallysuspected to be having squamous cellcarcinoma of the conjunctiva which washistopathologically proven on excisional biopsywith frozen section.

Fig.2 - molluscum contagiosum

Fig.3 - Conjunctival Squamous Cell Carcinoma

Dysplasia Scleral invasion of CA

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One patient, a 30 year old male presentedwith secondary cataract following anterioruveitis.

Though twenty six patients had anterioruveitis, it was most commonly secondary tocytomegalovirus retinitis, or due to herpeszoster ophthalmicus and idiopathic in onlytwo cases.

Discussion:

As 70% of AIDS patients eventuallydevelop ocular complications, the role of theophthalmologist in the management of a HIVpositive patient is becoming increasinglyimportant. The first ophthalmic report aboutpatients with ocular diseases attributed toAIDS in India was published in 1995. 6

In our study, the majority of patientswere men, in the 20-40 years age group. Thisis also reflected in the national statistics. 10

Heterosexual exposure to commercial sexworkers was the most common risk factor forHIV infection.

Ocular manifestations of HIV infection inany geographic area depends on a number offactors including the availability of health carefacilities and the prevalence of the diseasepatterns. The most common ophthalmicopportunistic infection in our study was CMVretinitis.

Among the anterior segment manifesta-tions, the most common one in our study waslid infections(without posterior segmentmanifestations). Five patients in our study hadblepharitis. In countries with warm climates,the prevalence of Staphylococcus aureus isas high as 95% in lid cultures, 11 andsubclinical and mild infections are quitecommon. In our patients due to immuno-deficiency the infection was more severe andled to lid ulceration and extensive blepharitis.Such unusual lid infections should arouse thesuspicion of immunocompromised state of thepatient. These lesions also pose a risk oftransmission of HIV during the ophthalmo-scopic examination of these patients.

Molluscum contagiosum affects 10-20%of symptomatic HIV infected individuals.

Extensive molluscum contagiosum in theeyelid has been reported in patients withAIDS.12,13 There has been one case report ofa patient with epibulbar molluscumcontagiosum. 14

Herpes zoster ophthalmicus (HZO) isrecognised as a marker for HIV infectionparticularly in sub-Saharan Africa, where 92%of patients with HZO were found to be HIVpositive.15 In our study there were fourpatients with HZO. Of which only one patientpresented as healed keratitis with decreasedcorneal sensation and healed anterior uveitis,unlike other reports which state a higherincidence of corneal involvement in HIVinfected patients (89%versus 65%).16 A 17%incidence of acute retinal necrosis followingHZO in patients who were HIV positive hasbeen reported. One out of the four patientsdeveloped subsequent acute retinal necrosis.

Corneal epitheliopathy in the form ofphospholipidosis has been described in twopatients in which ganciclovir and acyclovirgiven systemically were implicated. 17 Ourstudy included a patient with a focus ofepithelial dysplasia with pigmentation withoutany evident cause.

Although rare, the HIV positive patientappears to be at a higher risk for anteriorsegment fungal infection. Keratitis due toCandida albicans infection has been reportedin AIDS patient without a history of traumaor use of topical corticosteroids. 18-20

Cryptococcal keratitis has been described ina 30 year old AIDS patient who also hadCryptococcal meningitis and disseminatedcutaneous lesions. 21 In our patient thecausative organism was Penicillium, detectedfollowing evisceration.

Squamous cell carcinoma is the thirdmost common neoplasm associated with HIVinfection, following Kaposi’s sarcoma andlymphoma.22 One patient in our studyunderwent successful excisional biopsy ofconjunctival squamous cell carcinoma withoutany recurrence over a 6 month period of followup. Unlike the US studies 1,23 we did notobserve Kaposi’s sarcoma of the eye.

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Stevens-Johnson syndrome (SJS) hasbeen reported following treatment withdapsone and trimethoprimsulphamethoxazoleas well as others in HIV infected patients. Inour study one patient developed SJS followingtrimethoprimsulphamethoxazole prophylaxis.Despite profound immunosuppression andalteration in cell mediated immunity, AIDSmay paradoxically show the development ofparticularly severe SJS and toxic epidermalnecrolysis including ocular features.24

Conjunctival microvasculopathy may bepresent in 75% of patients with AIDS and aresimilar to those seen in sickle cell disease.Theexact cause for this abnormality is not yetknown, though a number of theories havebeen speculated.

Anterior uveitis in AIDS patients occurssecondary to CMV retinitis, or due to herpeszoster, could be drug induced or idiopathic.

The prevalence of AIDS in India is at itsiceberg only and the focus has shifted fromthe developed countries to the underdevelopedareas. The epidemic will pose a challenge toall practitioners of medicine includingophthalmologists. Recognising these manifes-tations at an early stage, performingappropriate laboratory investigations and earlytreatment can help in reducing the morbidityand mortality of AIDS.

References:

1. Holland GN, Gotlieb MS, Yee RD. Oculardisorders associated with a new severeacquired cellular immune deficiencysyndrome. Am J Ophthalmol. 1982; 93;393-402.

2. Freeman WR, Lerner CW, Mines JA, LashRS, Nadel AJ, Starr MB and Tapper ML. Aprospective study of ophthalmologicfindings in acquired immunodeficiencysyndrome. Am J Ophthalmol 1984; 97;133-142.

3. Jabs DA, Green WR, Fox R et al. Ocularmanifestations of acquired immuno-deficiency syndrome. Ophthalmology 1989;96; 1092-1099.

4. Biswas J, Madhavan HN, George AE,Kumarasamy N, Solomon S. Ocular lesionsassociated with HIV infection in India : Aseries of 100 consecutive patientsevaluated at e referral center. Am JOphthalmol 2000; 129(1) 9-15.

5. Kestelyn P., Van de Penre P, Rourvoy Det al. A prospective study of the ophthalmicfindings in the acquired immunodeficiencysyndrome in Africa. Am J Ophthalmol1985; 100 : 230-238.

6. Biswas J, Madhavan HN, Badrinath SS.Ocular lesions in AIDS: A report of firsttwo cases in India. Indian J Ophthalmol1995; 43;69-72.

7. Biswas et al. Ophthalmic manifestationsof HIV/AIDS. Ind J Ophthalmol; 1999; 47;87-93.

8. Sahu D K, Namperumalsamy P,Rajalakshmi C. Ocular manifestations ofHIV infection / AIDS in South Indianpatients. Ind J Ophthalmol 1999; 47 : 79-85.

9. Jalali S, Rao UR, Laxmi V. Acute retinalnecrosis syndrome in an HIV positive case:the first case reported from India. Ind. JOpthalmol 1996; 44: 95-97.

10. National AIDS Control Organisation,Ministry of Health and Family, Governmentof India. Surveillance for HIV Infection/AIDS Cases in India: Ministry of Healthand Family Welfare, Government of India;1986-1997.

11. Tomar VPS, Sharma OP, and Joski K.Bacterial and fungal flora of normalconjunctiva. Ann Ophthalmol 1971;3:669

12. Kohn SR. Molluscum contagiosum inpatients with acquired immunodeficiency.Arch Ophthalmol 1987; 105:458.

13. Robinson MR, Udell IJ, Garber PF, PerryHD, Streeten BW. Molluscum contagiosumof the eyelids in patients with acquiredimmunodeficiency syndrome. Ophthalmology1992; 99; 1745-47.

14. Charles NC, Friedberg DN,. Epibulbarmolluscum contagiosum in acquiredimmunodeficiency syndrome. Ophthalmology1992; 99; 1123-36.

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15. Van de Perre P., Bakkers E., BatungwanaoJ. et al. “ Herpes zoster in African patients:An early manifestation of HIV infection.”Scand. J. Infect. Dis.20(1998),277-282.

16. Stenson S.Anterior segment manifestationsin AIDS. In : Stenson SM, FriedbergDN,eds. AIDS and the eye,vol 1.NewOrleans: Contact Lens Association ofOphthalmologists,1995:35-63.

17. Wilhelmus K., Keener M., Jones D. et al.”Corneal lipidosis in patients with acquiredimmunodeficiency syndrome.,” Am JOphthalmol. 119 (1995), 14-19

18. Shuler J, Engstrom R, Holland G. Externalocular disease and anterior segmentdisorders associated with AIDS. IntOphthalmol Clin 1989;29;98-104

19. Aristimuno B, Nirankari V, Hemady R,Rodrigues M. Spontaneous ulcerativeKeratitis in immunocompromised patients.Am J Ophthalmol 1992;115: 202-208.

20. Parrish C, O’Day D, Hoyle T. Spontaneousfungal corneal ulcer as a manifestation ofAIDS. Am J Ophthalmol1987;104:302

21. Muccioli C., Belfort R.M., Neves R. et al.“Limbal and choroidal cryptococcusinfection in the acquired immunodeficiencysyndrome,” Am J Ophthalmol.120 (1995),539-540

22. Winward K, Curtain V. Conjunctivalsquamous cell carcinoma in a patient withhuman immunodeficiency virus infection,Am J Ophthalmol 1989; 107 : 554-555.

23. Holland GN, Pepose JS, Petit TH, GotliebMS, Yee RD, Foos RY. Acquired immunedeficiency syndrome: Ocular manifesta-tions. Ophthalmology 1983; 90: 859-73.

24. Belfort R, de Smet M, Whitcup S et al.Ocular complications of Stevens-JohnsonSyndrome and Toxic Epidermal Necrosisin patients with AIDS. Cornea 10 (1991),536-538.

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Bietti et al in 1955, described an unusualdegenerative corneal condition characterizedby deposition of yellowish globules in thesuperficial layers of the cornea. 1 Thiscondition was noted predominantly in menwho spent long periods of the time workingoutdoors. Initially termed as “Bietti’s cornealdegeneration”, this condition has beenassigned many names including “climaticdroplet keratopathy”, “Labrador keratopathy”,“chronic actinic keratopathy”, “elastoticdegeneration” and “spheroidal degeneration”.2

This condition usually begins at an older age,seen more frequently with increasing age anddoes not seem to have a familial propensity.However there are a few case reports inliterature that describe the rare occurrenceof this condition in families.3-5

We describe the familial occurrence ofbilaterally symmetrical primary band-shapedspheroidal degeneration of the cornea in twosiblings.

Case reports:

Case 1

A 37-year-old male presented to ourclinic in June 2001 with the history ofprogressive visual loss in both eyes associatedwith photophobia, irritation, and wateringsince the age of 15 years. The patient hadundergone corneal scraping in both eyes 7years back followed by a significantimprovement in both his symptoms and visualacuity. The general health of the patient waswithin normal limits with no relevantoccupational or environmental history.

On examination his best-corrected visualacuity (BCVA) was counting fingers at ½ meterin both eyes. Slit lamp examination revealed

presence of sub epithelial and anterior stromalgolden yellow refractile globular deposits inthe interpalpebral area, extending on eithersides of the horizontal limbus onto theconjunctiva in both eyes. A small area ofcentral clearing was noted in the right eye.Superficial corneal vascularisation associatedwith minimal stromal scarring was also notedin the interpalpebral region. The epitheliumwas intact though irregularly elevated by theunderlying deposits. Corneal sensations werenormal. There were no other associated ocularabnormalities. Rest of the ocular examinationwas found to be normal.

A deep lamellar keratoplasty wasperformed in the left eye along with amnioticmembrane transplantation. Postoperatively hewas treated with topical corticosteroids andtear substitutes. At last follow up two monthslater, his BCVA in the left eye had improvedto 6/12.

Case 2:

The elder sister, 38 years old presentedwith a similar history. On examination herBCVA in the right eye was 6/24; and handmovements close to face in the left eye. Slitlamp biomicroscopy of the eyes revealedsimilar clinical picture of a central band ofgolden yellowish spheroidal deposits in theanterior stroma involving the interpalpebralarea and extending on either side on to theconjunctiva in both eyes. (Fig 1) The centralcornea was spared above the visual axis inthe right eye. Large nodules with irregularelevation of overlying epithelium were notedin the left eye. Corneal sensations and rest ofthe ocular examination was within normallimits.

Familial band-shaped spheroidaldegeneration of the cornea, report of twocasesGeetha K Iyer, Rajesh Fogla & Jyotirmay Biswas

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A deep lamellar keratoplasty wasperformed in the left eye. At last follow up sixweeks later, her BCVA had improved to 6/24in the left eye and slit lamp biomicroscopyrevealed a clear lamellar graft. (Fig 2)

Histopathological findings of the cornealtissue obtained during surgery in both thecases, revealed basophilic globular depositsin the anterior stroma, thinning of theepithelium and destruction of the Bowman’slayer at places. The corneal globules had acharacteristic autofluorescence and stainingproperties with stains for elastin, which wereconsistent with diagnosis of spheroidaldegeneration.

Discussion:

Bietti,s original description of cornealdegeneration characterised by deposits ofyellowish, oily globules, although describedby a variety of terms, is most commonlyreferred to as spheroidal degeneration. 2

Fraunfelder and colleagues divided thiscondition into 3 basic forms: 1) primarycorneal type occurring bilaterally associatedwith increasing age and without any evidenceof prior ocular disease, 2) secondary cornealtype associated with preexisting ocularpathology, and 3) conjunctival type whereinconjunctival deposits are prominent with or

without corneal involvement. 6,7

Patients with primary corneal type havebilateral, golden yellow deposits in theinterpalpebral cornea, predominantly inelderly males who spend long periods of timeoutdoors. Initial corneal involvement beginsat the periphery and the central cornea isusually spared. Familial occurrence isextremely rare. 5

Our cases do not fit into the classificationdescribed by Fraunfelder et al. 6,7 Both thepatients were young, were siblings, and hadbilateral involvement of the central cornea,without any evidence of associated oculardisease. Based on history, the corneal changesseem to have started between the age of 15 -20 years. Both the patients underwent deeplamellar keratoplasty with good postoperativevisual outcome.

Meisler et al have reported similarfindings in three brothers, with early onset inlife, two of them in the third decade. Hida etal have also reported familial occurrence ofthis condition in three cases from twoconsanguineous families.

Although familial occurrence of primaryspheroidal degeneration is extremely rare,both our cases indicate that, there seems tobe a variant which has a familial tendency,

Fig2. Slit lamp photograph of the left eyefollowing deep lamellar keratoplasty

Fig 1. Slit lamp photograph of the left eyeshowing band-shaped spheroidal degenerationinvoving the interpalpebral region of the cornea

95

occurs early in life, with initial involvementof the central cornea. Lamellar keratoplastyis successful in restoring useful vision in thesecases.

References:

1. Bietti GB, Guerra P, Ferraris de GasparePF. La dystrophie corneenne nodulaire enceinture des pays tropicaux a sol aride;contributions cliniques et anatomo-pathologiques. Bull Mem Soc Fr Ophthalmol1955; 68:101-129

2. Gray RH, Johnson GJ, Freedman DA.Climatic droplet keratopathy. SurvOphthalmol 1992; 36: 241 – 253

3. Hida T, Akiya S, Kigasawa K, Hosoda Y.Familial band shaped degeneration of thecornea. Am J Ophthalmol 1984; 97: 651 - 52.

4. Meisler DM, Tabbara KF, Wood IS, AlvardoJA, Biswell R. Familial band-shapednodular keratopathy. Ophthalmology 1985;92: 217 – 222

5. Hida T, Akiya S, Kigasawa K, Hosoda Y.Familial band shaped degeneration of thecornea. Br J Ophthalmol 1986; 70: 347 –353

6. Fraunfelder FT, Hanna C. Spheroidaldegeneration of cornea and conjunctiva.1: Clinical course and characteristics. AmJ Ophthalmol 1972; 74: 821-828

7. Fraunfelder FT, Hanna C. Spheroidaldegeneration of cornea and conjunctiva.3: Incidence, classification and etiology.Am J Ophthalmol 1973; 76: 41 - 50

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Indocyanine green angiogram in tubercularchoroiditis - Case ReportRupesh V. Agrawal, Dipankar Das, Jyotirmay Biswas, K. Jagannath and H. N. Madhavan

two weeks. Her chest x-ray showed thepresence of military tuberculosis. She was onantituberculous treatment (Rifampicin 450 mgtab once daily, Isoniazide 300 mg once daily,Pyrazinamide 750 mg tab once daily) for thepast two weeks and on topical corticosteroid,cycloplegic and antiglaucoma eye drops fordiagnosis of choroiditis with secondaryglaucoma. She had ductal adenocarcinoma ofthe breast three years back for which sheunderwent excision and radiotherapy.

On examination her best corrected visualacuity in the right eye was 20/200 and in theleft eye was 20/20. Extraocular movementswere full, free and painless. On slit lampexamination there was circumciliarycongestion in the right eye, corneal haze andpresence of mutton fat keratic precipitates oncorneal endothelium. There was mild anteriorchamber reaction of 1+. Lens showed veryearly posterior subcapsular cataract. Therewere 2+anterior vitreous cells. Gonioscopyrevealed open angles with scattered peripheralanterior syenchiae and increased pigmentationof the trabecular meshwork in both eyes. Theleft eye was normal on slit lamp examination.Applanation tension was 16 and 14 mm ofmercury in right and left eye respectively. Ondilated fundus examination media haze dueto significant vitritis was noted in the righteye (Fig.1A). The disc and macula were notvisualised clearly. Active choroiditis patch halfdisc diameter in size nasal to the disc wasnoted in the left eye (Fig. 2b) with normaldisc and macula (Fig. 2A).

Laboratory investigations revealederythrocyte sedimentation rate of 33 mm atend of one hour, normal sarcoid work up(serum calcium 8.0mg/dl, inorganicphosporus 4.1mg/dl, total protein 6.8mg/dl,albumin 3.5gm/dl, globulin 3.3gm/dl, A/G

Introduction:

Indocyanine green angiography (ICGA) isa newer diagnostic imaging technique whichemploys the use of a tricarbocyanine dyewhich has its peak absorption andfluorescence in the near infrared range.1 It isused mainly in the diagnosis and accuratetopographical localisation of occult choroidalneovascular membranes. 1 ICGA has thepotential to become very useful in the field ofinflammatory disorders of the choroid. Thedifferent findings of indocyanine greenangiography in chorioretinal inflammatorydisorders was documented by Guyer et al. 2

The typical findings of ICGA in acute posteriormultiple placoid pigment epitheliopathy,serpiginous choroiditis, birdshot retino-choroidopathy, multiple evanescent white dotsyndrome and Vogt Koyanagi Haradasyndrome have already been documented. 2,3

Herbert et al have described a case ofpresumed tuberculous choroio retinitis whichon indocyanine green showed unevenly sizedand irregularly distributed hypofluorescentdots & areas in the intermediate phase. Inthe late phase some of the hypofluorescentareas became isofluorescent & some areas oflocal hyperfluorescence were also seen. 4 Thecombination of FA with ICG could help inreaching the most accurate differentialdiagnosis in cases of chorio-retinal diseases.5

We describe the fundus fluoresceinangiogram (FFA) & ICGA findings in a case ofmiliary tuberculosis of the choroid andcorrelate the angiographic findings withclinical presentation.

Case Report:

A 47 year old female presented to ourinstitute with pain and redness in the righteye of 2-3 months and decreased vision of

97

ratio 1.0), slightly increased serum lysozyme(540 units), serum angiotensin convertingenzyme 41.8 units, Anterior chamber tap wasnegative for mycobacterium tuberculosisgenome by PCR and acid fast bacilli were notseen on smear or subsequent culture.

Fundus fluorescein angiogram of theright eye was not possible due to the presenceof vitreous haemorrhage. Left eye showednormal fluorescence temporal to the disc (Fig. 2E, 2F) and a hyperfluorescent lesion seeninferonasal to the disc (Fig. 2G) correlatingwith the active choroiditis lesion seenclinically. However in early phase ofindocyanine green angiogram there waspresence of an additional hypofluorescentlesion seen supertemporal to the macula ( Fig.2C) along with the hypofluorescent lesionpresent inferonasal to the disc ( Fig. 2D) whichwas seen clinically and on fluoresceinangiogram. The lesion inferonasal to the discshowed hyperfluorescence in the late phaseof ICGA (Fig. 2I) and the one presentsuperotemporal to the macula was remainedhypofluorescent (Fig. 2H).

Two months later her best correctedvisual acuity improved to 20/20 in right eyeand 20/20 was maintained in the left eye withcomplete resolution of the vitiritis in right eyeand normal disc and macula in the right eyeas well (Fig. 1b). She was asked to stop topical

steroids and to continue topical antiglaucomadrops in the right eye. In consultation withchest specialist she was asked to continuetwo drug regime (tab Rifampicin 450mg oneper day, tab Isoniazide 300mg one per day)for her systemic disease.

Discussion:

Indocyanine green angiography has beenfound to be beneficial in various posteriorsegment inflammatory disorders like acuteposterior multiple placoid pigmentepitheliopathy, birdshot retinochoroidopathy,multiple evanescent white dot syndrome,serpiginous choroiditis and Vogt KoyanagiHarada syndrome.2,3 In general, two mainpatterns of hypoflourescence has beendescribed by Herbert et al in choroiditisirrespective of its activity: (i) thehypoflourescenct areas to be present in allthe phases of angiography due tochoriocapillaries non-perfusion (ii)hypofluorescence in the early and intermediatephase of ICGA and later isofluorescence orhyperfluorescence.3

Tuberculosis is one of the leading causeof infectitious posterior uveitis in India.Establishing the diagnosis and attributing itto tuberculosis is often not possible. It isbased on purified protein derivative skin test,abnormal chest x-ray, isolating the organismfrom ocular fluid or other tissue. In the

Fig. 1A: Fundus photograph of the right eyeshowing dense vitritis with hazy view of thedisc and retina.

Fig. 1B: Fundus photograph of the right eyeafter two months of antitubercular therapy. Discand macula are normal.

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present case aqueous aspirate was negativefor mycobacterium tuberculosis by polymerasechain reaction as the organism can remainlocalised in the choroid and therefore remainundetected. We however feel the case isconsistent with military tuberculosis owing tothe military tubercles seen on chest X-Ray,

the presence of characteristic choroidal lesionand moreover complete resolution toantituberculosis therapy.

In the present case, dual angiogramrevealed the area of active choroiditis in formof hyperfluorescent lesion. However,indocyanine green angiography was able to

Fig. 2A: Fundus photograph of the left eye with normal disc and macula.Fig. 2B: Fundus photograph of left eye showing active choroiditis lesion inferonasal to the disc.Fig. 2C: Early ICGA of the left eye showing hypofluorescent lesion superotemporal to the macula.Fig. 2D: Early ICGA of the left eye showing hypofluorescent lesion inferonasal to the disccorresponding with lesion seen clinically and on fundus fluorescein angiogram.Fig. 2E: Early FFA of the left eye showing normal fluorescence of the posterior pole with nochoroidal lesion.Fig. 2F: Mid FFA of the left eye showing normal posterior pole fluorescence with no evidence ofchoroidal lesion.Fig. 2G: Mid FFA of the left eye showing hyperfluorescent lesion inferonasal to the disc.Fig. 2H: Late ICGA of the left eye showing hypofluorescent lesion superotemporal to macula.Fig. 2I: Late ICGA of the left eye showing hyperfluorescent lesion inferonasal to the disc.

2

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pick up more areas of involvement, which werenot seen on fundus fluorescein angiogram. Ithence delineated the disease process precisely.Indocyanine green angiography can thereforebe a useful adjunct in establishing theanatomical diagnosis of the disease anddelineating the same.

References :1. Bischoff PM, Flower RW: Ten years

experience with choroidal angiographyusing Indocyanine green dye: a newroutine examination or an epilogue? DocOphthalmology, 1985; 60: 235-291.

2. Guyer DR et al. Digital indocyanine greenangiography in chorioretinal disorders.Ophthalmology, 1992; 99: 287-290.

3. Herbert CP. Posterior uveitis: new insightsprovided by indocyanine greenangiography. Eye, 1998; 12: 757-759.

4. Wolfensberger TJ, Piguet B, Herbort CP.Indocyanine green angiographic featuresin tuberculous chorioretinitis. Am JOphthalmol; 1999; 127: 350-3.

5. Bischoff PM et al: Simultaneousindocyanine green and fluoresceinangiography. Retina, 1995.15: 91-99.

AN APPEALA lot of things in this world depend on money - security, shelter, education and evenhealth. But at Nethralaya, money has ceased to be a pre-requisite for sight.Day after day, year after year, Nethralaya treats hundreds of patients absolutely freeof cost and gives them back their sight. Treatment is provided free of cost to allpatients with a monthly income below Rs.1,750/-.Yet there is no discrimination between the free patient and the one who pays. Apartfrom the treatment, food, medicines and travel expenses are absolutely free.Those free patients depend on Nethralaya, and Nethralaya depends on you.So, come and join the OPHTHALMIC MISSION TRUST.For questions about tax exempt status and contributions, please contact:

Mr S V Acharya,Treasurer

Ophthalmic Mission Trust Inc. (OM Trust)14613, Pommel Drive, Rockville,

MD 20850, U.S.A.Phone: (301)251 0378

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For those of you in India and elsewhere, please contact:Dr S S Badrinath,

President & ChairmanSankara Nethralaya

(UNIT OF MEDICAL RESEARCH FOUNDATION)18 College Road, Chennai 600 006

Phone: 826 1265, 827 1616Fax: (044) 825 4180, 821 0117

INTERNET e-mail : chairman@sankaranethralaya.orgLOOK US UP ON THE WEB at http://www.sankaranethralaya.org

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Introduction:

Current treatment options for uvealmelanoma include enucleation, brachytherapy,charged particle radiotherapy, local resection,laser photocoagulation and observation. Inrecent times, Transpupillary Thermo Therapy(TTT) has evolved as a less morbid treatmentfor relatively small to medium sized posteriorchoroidal melanoma 1-6 .

In the collaborative ocular melanomastudy, 25% of the small tumors that wereobserved without treatment increased tobecome medium or large tumors over a 5-year follow-up. 2 tumors increased after 5years.7 It is thus preferable to treat smallmelanomas rather than observe them,especially if they show signs of activity. Smallmelanomas can be managed with relative easewith laser photocoagulation and TTT incontrast to the medium or large tumors, whichmay need brachytherapy or enucleation.

Uveal melanoma is relatively rare inAsian Indians and most patients presentinitially with large tumors necessitating

enucleation. We treated 6 Asian Indianpatients with small choroidal melanoma withTTT and present our results.

Patients and methods:

A retrospective analysis of the caserecords of six patients with choroidalmelanoma treated with transpupillarythermotherapy at our tertiary care centrebetween 1998 to 1999 was done. Individualtumor characteristics are outlined in table 1.2 patients had been treated with diode laserphotocoagulation earlier. The pupil was dilatedwith phenylephrine 5% and Tropicamide0.25% eye drops prior to treatment. TopicalLignocaine HCl 4% or retrobulbar injection ofLignocaine HCl 2% was used for anesthesia.Transpupillary thermotherapy was performedusing infrared diode laser at 810nm (OculightSL Diode photocoagulator with operatingmicroscope adapter) through a contact lens(Mainster lens: Ocular instruments, Bellevue,WA, USA.). A 2.0mm spot size was used andthe power was titrated to achieve a mildgraying of the tumor at the end of one minute.

Transpupillary Thermotherapy for ChoroidalMelanoma in Asian Indian PopulationMahesh. P. Shanmugam and Rajiv Raman

Table 1: Tumor characteristics

S.No Age Eye Location SRF Drusen Pigment Dimensions (Ht x V x H)1 72 OS Fovea just spared - + - 4.3 x 9.2 x 10.6 mm

2 67 OD Subfoveal - - - 3.4 x 12.8 x 10.4 mm

3 30 OD 1DD ST to disc + + + 2.5 x 5.9 x 7.1 mm

4 35 OS Just SN to disc + - - 4.2 x 9.1 x 9.3 mm

5 37 OS 1DD IT to disc - - - 3.3 x 7.4 x 12 mm

6 55 OS Just IT to disc - - - 2 x 5.1 x 5.1 mm

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Using the adjusted power and 2.0mm spotsize, entire surface of tumor including1-1.5mm of clinically normal chorioretinaaround the margins of the tumor was treatedby overlapping spots of one-minute duration.The location of the tumor, pre and posttreatment dimensions of the tumor on ultra-sonography, treatment parameters, adjunctivetreatment used before and after transpupillarythermotherapy and complications of therapywere noted on each follow up.

Results:

Average age at presentation of thechoroidal melanoma in this subset of patientswas 49.3 ± 17.3 years (range: 20 –72yrs )

with a male preponderance (M: F 5:1). Meanfollow-up was 11.5 ± 5 months (range: 2-22months). The mean pretreatment height of thetumor was 2.9 ± 0.78mm and the basaldiameter 9 ± 2.3mm. In 4 cases the tumorwas located within 1 disc diameter of the discand in 2, the tumor was located in the fovealand parafoveal areas respectively. Mean laserpower used was 885 ± 230.98MW, for anaverage duration of 16.83±7.41minutes (Table2). 5 of 6(83.3%) tumors showed signs ofregression after TTT (mean post treatmentheight: 1.18±1.09mm) (Fig. 1-5). One patient(case 4) did not respond to treatment andunderwent enucleation. The tumor residuewas treated with diode laser photocoagulation

(Iridex Oculight)in 2 patientsand 3 patientsu n d e r w e n tfurther TTT. Theaverage time toachieve a flatscar was 17months. Therewas no evidenceof metastaticdisease in anyof the patientsto date.

Table 2 : Treatment parameters with anatomical & visual results

S.No Ht. Before Tt Pre Tt Vn Power (mw) Spot size Duration Ht. at last Visit Post Tt Vn

1 2.6mm .6/18 800-1000 2mm 15min flat .6/9

2 3.4mm .6/60 500 2mm 25min 1.7mm .3/60

3 2.5mm .2/60 1000 2mm 25min 2.2mm .3/36

4 4.2mm .6/9 1200 2mm 27min Enucleated

5 2.7mm .6/18 800-1000 2mm 10min 2mm .6/30

6 2mm .6/36 810 1.2mm 10min flat .6/60

00.5

11.5

22.5

33.5

44.5

Fig 1 :Comparison of height of the tumor before & after Tt.

pre Tt Ht. 2.6 3.4 2.5 4.2 2.7 2

Post Tt Ht. 0 1.7 2.2 Enucleated 2 0

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thicker tumors (mean height:: 8.4mm) 8.Schnelder et al evaluated treatment ofchoroidal melanoma in 17 patients eitherusing transpupillary thermotherapy alone (6eyes) or combined brachytherapy andtranspupillary thermotherapy (11 eyes). Alltumors exhibited a reduction of tumor heightafter a mean follow up of 14.25 months. 4

Godfrey et al have also shown 71.4% tumorsregressed with TTT over 8.7 months.5 Shieldset al reported a reduction of tumor heightfrom 2.8mm to 1.7mm in 100 patients, sixmonths after TTT. Tumor regression occurredin 94% cases with an average of three sessionsof treatment.6 Other studies have also shownthe efficacy of TTT in tumors with a meanheight of 2.76mm and basal diameter of6.83mm. 1-6 In our series 83.3%of tumors witha mean height was 2.9mm and basal diameter9.0 mm responded favorably to TTT.

Figure 2 : Fundus photograph showing activetumor. (Pt.5)

Figure 3 : USG B scan prior to TTT (Pt. 5)

Discussion

Hyperthermia has a relative selectiveeffect on neoplastic tissue. The impairedcooling system of the tumor due to the absentor aberrant vascular channels makes thetumor act like a heat sink. Journee-de-Korveret al first described intermediate hyperthermiawithin the temperature range of 45-60 0Cresulting in necrosis upto a depth of 3-4mmof the tumor, whereas hyperthermia above600C (temperature achieved in laserphotocoagulation) resulted in limitedsuperficial penetration.2 This ability of TTT topenetrate to a depth of 3-4 mm, makes it anideal treatment modality for small melanomas.

Hyperthermia has been used to enhancethe effect of radiation in the treatment ofchoroidal melanomas 1,2. Oosterhuis et al havecombined brachytherapy with TTT to treat

Figure 4 : Fundus photograph showing scarringof tumor and flattening of lesion after TTT

Figure 5 : USG B scan post TTT in the samepatient.

3 4

5 6

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One patient who did not respond to TTT(case 4) had an amelanotic tumor, lackingadequate pigment to absorb laser energy.Shields et al have also shown that amelanotictumors do not respond well to TTT, untilretreated with indocyanine green as anadjunct to enhance laser absorption. Godfreyet al found that increasing the power alonedoes not have the desired result in amelanotictumors.5 In addition, this eye which wasenucleated had a medium sized tumorcomposed of epithelioid cells onhistopathological examination establishing itshigher malignant potential.

3 patients in our series had decreasedvision after TTT, because of the proximity ofthe tumor to the optic nerve or macula. Visualacuity may improve in some cases withabsorption of subretinal fluid in an extramacular tumor, but most submacular orperipapillary tumors lose vision due to heatrelated damage. Shields et al reported a stableor improved vision in 58% cases while Godfreyet al reported reduced vision in 43% cases.Other complications associated with TTT areretinal vascular occlusions, scarring withtractional changes, thermal papillitis, minimalsubretinal or vitreous hemorrhage.

Laser photocoagulation has a poor depthpenetration and has to be applied in multiplesittings to treat small melanomas. TTT has abetter depth penetration thereby obviating theneed for multiple treatments. In addition, itcan be used to treat tumors that are largerthan that can be treated with laserphotocoagulation but too small to employbrachytherapy. Brachytherapy is associatedwith severe complications such as radiationretinopathy, papillopathy, cataract, dry eyeetc., in addition to the need for surgery toapply and remove the plaque. TTT avoids thesecomplications and is a viable alternative insmall and selected medium sized tumors.

However, long term effects of TTT are asyet unknown and heat induced damage toocular structures may not become clinicallyevident for months or years, similar toradiotherapy. TTT alone cannot be used totreat most medium and large tumors or those

situated in the periphery. Currentrecommendations for TTT are melanomas< 4mm in height and < 7 mm in basal diameter.

This is the first report to evaluate therole of TTT for choroidal melanoma in AsianIndian patients. This report also assumessignificance as I125 Brachytherapy for treatingmelanomas is as yet not available in Indiaand some of the tumors that may needbrachytherapy may alternatively be managedwith TTT.

Reference:1. Oosterhuis J A, Journee-de Korver H G,

Kakebeeke-Kemme H M. Transpupillarythermotherapy in choroidal melanomas.Arch Ophthalmol 1995;113:315-321

2. Oosterhuis J A, Journee-de Korver H G,Kakebeeke-Kemme H M. TranspupillaryThermotherapy; results in 50 patients withchoroidal melanomas. Arch Ophthalmol1998;116:157-162

3. Nuijs-Beems E M, Oosterhuis J A, Verburg-van der Marel E H et al. Tumor destructionby intermediate level hyperthermia. CurrEye Res 1990; 9: 771-790

4. Schnelder H, Fischer K, Fletkau R et al.Transpupillary thermotherapy of choroidalmelanomas. Klin – Monatsbl –Augenhellkd. 1999;214(2):90-5

5. Godfrey D G, Waldron R G, Capone A.Transpupillary thermotherapy for smallchoroidal melanoma. Am J Ophthalmol1999;128:88-93

6. Shields C L, Shields J A, Cater J et al.Transpupillary thermotherapy for choroidalmelanomas: tumor control and visualresults in 100 consecutive cases.Ophthalmology. 1998;105(4):581-590

7. Collaborative Ocular Melanoma StudyGroup. Factors predictive of growth andtreatment of small choroidalmelanoma.Arch Ophthalmol 1997;115:1537-1544

8. Keunen JE, Oosterhuis JA, Journee-deKorver HG. Transpupillary thermotherapyof choroidal melanomas with or withoutbrachytherapy :a dilemma. Br-J-Ophthalmol.1999;83(11):1212-3

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Introduction

Convergence insufficiency, characterizedby receded near point of convergence and alarger exodeviation for near than for distance,is by far the most commonly encounteredbinocular vision ailment in an orthoptic clinic.Convergence insufficiency is an anomaly inwhich both the accommodation and vergencesystem and their complex interplay thus haveto be thoroughly examined before arriving atthe diagnosis of convergence insufficiency.Case report details are the presentation,examination, treatment and outcome of apatient with convergence insufficiency.

Case ReportA 27-year-old Ophthalmologist was

referred to the Orthoptic Clinic of SankaraNethralaya with chief complaints of doublevision when performing eye surgery. He hadno complaints with vision for distance andnear.

Ocular examination showed distanceacuities of 6/5 and near acuities of N6 inboth eyes with his existing myopic andastigmatic correction. Subjective and objectiverefraction revealed a minor and insignificantchange in the astigmatic correction in the lefteye. No diplopia or suppression was reportedwith Snellen acuity and Worth–4-Dot test.Anterior and posterior segments of both eyeswere normal. Orthoptic evaluation showednormal extra ocular motility. Cover test withthe spectacles revealed an orthophoria fordistance and an exophoria with anintermittent divergent squint (IDS) for near.These were substantiated by the phoriameasures for both distance and near. The nearpoint of convergence (NPC) was receded bothobjectively (16 cms) and subjectively (14cms).Relative amplitudes were also reduced when

compared to a normal age matched individual(NRA: +2.50DS; PRA: -1.50DS). The normalNegative relative accommodation is +1.75DSto +2.00DS and the normal Positive relativeaccommodation is –2.25DS to –2.50DS.Dynamic retinoscopy showed a lag ofaccommodation of +1.00DS OU. The vergencelimits, as measured by synoptophore, werealso borderline (table 1). Binocularaccommodative facility was within normallimits (17 cycles /min) Stereopsis thresholdmeasured by the Random Dot stereopsismethod showed a degraded stereopsisthreshold of 80 arc sec (table: 4). Thesefindings suggested a diagnosis of convergenceinsufficiency and depleted fusional vergenceranges. The patient was advised to undergovergnce training (one sitting per day lasting15 minutes on synotophore) for 10 days andhome vision therapy exercises for improvingconvergence (Cat-card exercises and Pencilpush-up exercises – 2 times per day lasting15 minutes each) until the next visit.

DUCTION BLUR BREAK RECOVERY Adduction +15° +20° +14° Abduction - -5° -1° Table 1: Vergence ranges in first visit

The patient felt much better after 10 daysof vergence exercises but still had problemswhile performing surgeries. There was nochange in the phoria status when comparedto the last visit. The near point of convergencehad improved both subjectively and objectively(8cms). The lag of accommodation remainedthe same but the accommodative facilityimproved to 26 cycles per min when comparedto the first visit. It was interesting to note animprovement in the vergence ranges especiallyin the “Break” values of the abduction–adduction testing (Table2). A remarkable

Degraded stereopsis as a presenting sign ofConvergence InsufficiencyS.Jayarajini and Shrikant R Bharadwaj

105

improvement in the stereopsis threshold from80 arc sec to 20 arc sec was also noted (Table4). The patient was asked to continue homevision therapy (2 times a day lasting 15mins.each) until the next follow-up.

DUCTION BLUR BREAK RECOVERY Adduction +21° +31° +28° Abduction - -5° -1°

Table 2: Vergence ranges in second visit

One month later the patient showedsignificant improvement in his performancewith the operating microscope. Orthopticevaluation during this session revealed anorthophoria for both distance and nearconfirmed Maddox rod findings. The near pointof convergence had further improved upto 5cms. (Objectively and subjectively). Asignificant improvement in both the nearpoints of accommodation and the relativeaccommodation (NRA: +3.25DS ; PRA: -5.00DS) was noted . The accommodativefacility showed a small and insignificantdecrease since the last visit. The responseaccommodation was same as the last visit (Lagvalues of OD: +0.75DS; OS: +1.00DS). Similarto the last visit, the “Break” values showedthe maximum change when compared to theprevious visits, although an overall increase

in the “ Blur” and “Recovery” values was alsonoted (Table3). Interestingly, the stereopsisthreshold remained the same as the last visit(20 arc sec) (Table 4). The patient was advisedto continue home vision therapy as amaintenance measure.

DUCTION BLUR BREAK RECOVERY Adduction +20° +36° +30° Abduction - -7° -4°

Table 3: Vergence ranges in third visit

DiscussionConvergence insufficiency is generally

regarded as a syndrome which includes anexodeviation of the eyes at near point,relatively little or no deviation of the eyes withdistance fixation, a relative deficit of thepositive relative convergence and a recedednear point of convergence. 1 Studies onvergence anomalies places convergenceinsufficiency as the leading cause ofaesthenopia and ocular fatigue 2, with theincidence rate ranging from 1.75% to 25% inAmerican population. 3,4 This deficiency canoften present as other vergence anomaliessuch as convergence excess, divergenceinsufficiency, divergence excess and false

Test parameters First visit Final visit Normal values Cover test Orthophoria for

distance; IDS for near

Orthophoria for both distance and near

Orthophoria for both distance and near

Near point of convergence

Subjective: 14 cms Objective: 16 cms

Subjective: 5cms Objective: 5 cms

Subjective: 8cms Objective: 8cms

Near point of accommodation

Push up : 12 cms Push out : 12 cms.

Push up : 8 cms Push out : 8 cms.

Push up:13cms Push out:13cms

Lag of accommodation

OD:+1.00DS OS:+1.00DS

OD:+0.75DS OS:+1.00DS

OU: +0.75DS to +1.00DS

Relative accommodation

NRA:+2.50DS PRA:-1.50DS

NRA:+3.25DS PRA:-5.00DS

NRA:+1.75DS to +2.00DS PRA:-2.25DS to -2.50DS

Accommodative facility

17 cycle/minute 23 cycle/minute 12 cycles/min

Stereopsis thresholds

80 arc seconds 20 arc seconds 40 arc seconds

Table 4: comparison of the various test parameters in the first and final visit

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convergence insufficiency and thus should beapproached with caution. The variousoculomotor parameters should be thoroughlyanalyzed before the treatment modality isdecided upon.

The end-point of convergence is Diplopia,which marks the exhaustion of both theaccommodative and fusional convergencelimits (effect of tonic and proximal convergenceis negated). The demand on convergence ismet either by the accommodative convergenceor by the fusional convergence. Deficiency inone of the two components is usuallycompensated by the other for the maintenanceof normal binocular vision.

Dynamic retinoscopy on the first visitrevealed a decreased accommodation of+2.00DS (OU) for a demand of +3.00DS. Theaccommodative convergence was thusdecreased and an additional strain on thefusional vergence system was put to meet thedemands on convergence. Borderline vergenceranges during the evaluation revealed a poorfusional vergence range. Thus, the demandon convergence was not sustained, therebyleading to diplopia and degradation inStereopsis thresholds. This probably was thereason for the poor performance of the patientwith surgical microscopes. The lag valueshowever should be interpreted with caution.Convergence insufficiency is usuallyassociated with low lag values (increasedresponse accommodation) to compensate forthe poor fusional reserves.5 The 40cm unfuseddynamic retinoscopy would tend to exhibit anormal or high lag because, monocularly, the

accommodation may be unaffected byconvergence.5

Orthoptic evaluation on the subsequentvisits revealed an improved near point ofconvergence and vergence values (Graph1).The lag of accommodation remained the samepointing a steady state of accommodativeconvergence. The improved near point ofconvergence was more because of the fusionalvergence involvement. This is in accordancewith the study done by Daum. 6 The result isfurther corroborated by the improved “breakvalues” in adduction. The Stereopsisthresholds improved near point of convergenceand improved fusional reserves (Graph2).

Low relative amplitudes ofaccommodation, as measured in the initialevaluation do not essentially imply lowaccommodative thresholds. Poor fusionalreserves can often cause a Diplopia to occureven before the sustained blur is obtained.5Further, presence of an accommodative facilityof 17cycles / min contradicts a pooraccommodative reserve. The phoria statusimproved over the course of treatment. Schoraccounted for changes in phoria positionbecause of slow fusional vergence 7 and thisprobably explains the change in the phoriastatus.

Treatment of convergence insufficiencylargely depends upon two things:

1. Full compensation of heterophoria, whichis not likely to cause any symptoms.

2. Partial compensation of heterophoria,which is likely to cause symptoms.

Stereopsis Threshold

0102030405060708090

Trial 1 Trial 2 Trial 3

Graph 2: Comparison of stereopsisthreshold in the three visits

Vergence limits

05

10152025303540

Trial 1 Trial 2 Trial 3

Graph 1: Comparison of vergence limitsin the three visits

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Thus, treatment is indicated only in thoseconditions in which the heterophoria is notfully compensated. 8 The success rate intreatment of exodeviations has been found tobe generally very good in latent and mostintermittent deviations treated with orthoptics,especially those of convergence insufficiency.9

It is interesting to note that orthoptics caninfluence slow fusional vergence.10 The datain this paper confirm that orthoptics can affectthe heterophoria value because of effects onthe slow fusional vergence system. Orthopticsis usually effective at strengthening thevergence system and had only an insignificanteffect on the normal portion of the system. 11

Treatment, thus should be aimed at improvingboth the facilities and aid a harmoniousinteraction of the two systems. Animprovement in the AC/A component andother ocular parameters following orthoptictreatment and a subsequent decrease in theirfacility after one year of therapy. This suggeststhat the treatment provided to improve thepatient`s condition should not be stoppedupon achievement of desired results butshould be tapered slowly for maintenance ofthe same.

References

1. Duke-Elder S, Waybar K Ocular motilityand Strabismus, Duke-Elder S,Ed.Systemof Ophthalmol and Vol.6 St. Louis: CVMosby 1973: 564-72.

2. Daum KM Characteristics of ConvergenceInsufficiency, Am J Optom Physiol opt,1988; 65(6): 426-438.

3. Norm MS ConvergenceInsufficiency:Incidence in ophthalmicpractice.Results of orthoptics treatment,Acta Ophthalmol ,1966; 44: 132-38.

4. Kratka Z, Kratka WH ConvergenceInsufficiency; its frequency andimportance,Am J Orthop,1956;6: 73-3.

5. Borish IM Clinical Refraction,3rdEd,1970,Chicago,814-816

6. Daum KM Characteristics ofExodeviations:II.Changes with treatmentwith Orthoptics, Am J Optom Physiol opt,1986,63(4): 244-51.

7. Schor CM The influence of rapid prismadaptation upon fixation disparity,VisionRes,1979;19: 757-65.

8. Lyle and Jackson's Practical orthoptics inthe treatment of squint,5th Ed, JaypeeBrothers,New Delhi,1994,424-429.

9. Dalziel CC Effect of vision training onpatients who fail Sheard's criterion, Am JOptom Physiol opt,1981;56:78-81.

10. Sheedy JE Fixation disparity analysis ofoculo-motor imbalance, Am J Optom Physiolopt,1980;57:632-9.

11. Daum KM The course and effect of visualtraining on the vergence system, Am JOptom Physiol opt,1982;59:223-7.

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within or across databases. Numerous humangenetics and molecular biology databases arecurrently providing such links.

The human genome database is acompilation of various databases, which givesinformation on the various aspects of thehuman genome. These databases can be usedto compare and analyze our observed data.Chromosomal abnormalities, mutation

analysis, linkage analysis and informationregarding hereditary disorders can be got fromthese databases.

In this paper we discuss how we exploredthe web to compile the human genomicdatabases so that it can be effectively used inour laboratory. In our laboratory, we areworking to understand the fundamentalgenetics of various eye genetic disorders like

Search Engines

(www.google.com, www.webcrawler.com)

Databases

Education databases

Lab oriented databases

Clinic & patient related databases

www.hgmp.mrc.ac.uk http://gslc.genetics.utah.edu/ http://www.nimh.nih.gov/research/ http://www.univ.trieste.it/~biologia/ http://www-genome.wi.mit.edu/ http://research.marshfieldclinic.org/genetics/ http://www.chlc.org/ http://www.geneclinics.org/

www.irpa.org www.blindness.org www.focusnewsletter.org www.rbsociety.org www.graylab.ac.uk/cancaenet www.eyecancer.com www.ndss.org www.sdsa.org.uk www.deafblind.co.uk

www.gdb.org www.bioscience.org http://bioinformatics.weizmann.ac.il/udb/ http://genome.wustl.edu http://genome.cse.ucsc.edu/ www.hgmp.mrc.ac.uk www.cf.ac.uk www3.ncbi.nlm.nih.gov/omim/

Figure:1 Human genome related World Wide Web sites.

(contd. from page 112)

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age-related cataract, angle closure glaucoma,diabetic retinopathy, retinoblastoma, retinitispigmentosa and other retinal degenerativedisorders. We also searched for DNA softwareprograms that can be identified anddownloaded so that it can be useful for geneticstudies.

Methodology:

The details about various human genomedatabases and the free software tools areobtained by browsing the Internet with thehelp of the various search engines likewww.google.com, www.yahoo.com,www.metacrawler.com, www.netcrawler.comand www.altavista.com. For the search weused keywords like DNA databases, humangenome database management and researchgenetics. This search and analyses took fourweeks between start and completion.

Results and Discussion: On search wefound that 106 independent databases wererelated to the human genome. The databaseswere on various aspects of human genomelike chromosomal location of genes, disordersassociated with chromosomal abnormality,single gene disorders, structure of the gene,domains in the gene, current research onvarious hereditary disorders etc. Thusobtained databases were classified into clinicaland laboratory related databases. The clinicaldatabases were linked only to ocular disordersand were further sub-classified into academicand patient related genetic databases. Thedatabases giving information on the currentresearch on ocular genetic disorders wereincluded in the academic section while thoseinformation oriented towards patients’education were included in the patient relateddatabase sections. These databases also helpthe clinician to counsel the patients. Thelaboratory related search focused on thedatabases with software tools, which can beused for submitting DNA sequences, findingout mutation, human genome loci,polymorphism, probes, genetic maps, citationsand references. Various databases obtainedare dealt in the following sections and a listis provided in Figure 1.

The www.hgmp.mrc.ac.uk givesinformation on the current human genomeresearch. The Human Genome Project (HGP)is an international research effort tocharacterize the genomes of human andselected model organisms through completemapping and sequencing of their DNA, todevelop technologies for genomic analysis, toexamine the ethical, legal and socialimplications of human genetics research, andto train scientists who will be able to utilizethe tools and resources developed through theHGP to pursue biological studies that willimprove human health. Thegslc.genetics.utah.edu/index.html - GSLC alsocalled the Genetic Science Learning Centerhelps people understand how genetics affectsour life and society. It gives information onbasic genetics, genetic disorders, the geneticsrelated to the society and the thematic units.The www3.ncbi.nlm.nih.gov/Entez/ (NCBI) -is a database on sequence retrieval fromhyperlinked protein, nucleic acid, proteinstructure and genome mapping databases. Thewww.hgmp.mrc.ac.uk also gives informationon each chromosome and the centersassociated with it. The “www.gdb.org/gdb/hgp” is a Human Genome Project resource.The is one of the most important databasethat holds data on human genome loci,polymorphism, mutation, probes, geneticmarkers, Gen Bank, citations and contacts.

The “www.genome.wustl.edu” databasecollects records of chromosome abnormalitiesfrom over 70% of the laboratories performingroutine cytogenetic analysis in the UK. Therecords contain the karyotype of the sample,the primary reason for referral, the type oftissue sampled and the presence of a cell line/stored tissue. The Integrated GenomicDatabase (IGB) is an example of a molecularbiology data warehouse. Database federationsand data warehouses usually provide fullquery facilities and insulate users from thecomponent databases via their globalschemas. Multidatabase systems arecollections of loosely coupled databases, whichare not integrated using a global schema.

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The bioinformatics.weizmann.ac.il/udb/- The Unified Database (UDB) presents anintegrated map for each chromosome, basedon data integrated from various radiationhybrid, linkage and physical mappingresources. With the help of sequencedenhanced UDB we can get information on aregion in a specified chromosome, aboutmarkers and cytogenetic bands.

Software tools for DNA analysis: Thesedatabases provide programs which can beused in DNA analysis like searching for motifs,patterns in DNA sequences, analysis ofmicroarrays, selection of nucleotide probes etc.Wordup ( www.area.ba.cnr.it/pub/embnet/software/Wordup)- This is a fast and sensitivemethod designed to isolate short nucleotidesequence, which has non-random statisticalproperties and may thus be biological active.Coresearch ( www.gsf.de) - This programCoresearch is used to identify and delimitateconsensus elements (e.g. protein binding sites)in a set of unaligned nucleic acid sequences.The www.tigr.org- (The Institute for GenomicResearch) - this database provides over 15free softwares for different uses like, MUMmer -this is a system for aligning whole genomesequences. Using an efficient data structurethe system rapidly aligns sequences, whichcontains millions of nucleotides. TIGR MultipleExperiment Viewer- This software is a JAVAapplication used to allow the analysis ofmicroarray data to identify patterns of geneexpression and differentially expressed genes.Genesplicer - It is a fast and flexible systemused for detecting splice sites in the genomicDNA of various eukaryotes. GlimmerM- This isa gene finder based on a dynamicprogramming algorithm that considers allpossible exons for inclusion in a gene modeland chooses the best of these combinations.“www.cybergenome.com” -There are a lot ofsoftwares available in this sites like Primer3:(www-genome.wi.mit.edu/cgi-bin/primer/primer3_www.cgi) is primer selection softwarefrom MIT that considers oligo meltingtemperature, size, GC content, and primer-dimer possibilities; PCR size, and possibleconstraints within the source sequence. It was

developed at Whitehead Institute and HorwardHughes Medical Institute. DNA Tools(www.cybergenome.com/tools/software.htm) isa program package for routine handling andanalysis of DNA and protein sequences. Thepackage includes general facilities forsequence and contig editing, restrictionenzyme mapping, translation, repeatidentification, advanced options for searchingsequences and their headers. With the helpof this software several thousand sequencescan be loaded and analyzed in a single project.Trace Viewers: ABI chromatogram viewers forWindows and MAC platforms. PDRAW32: Thisis a DNA annotation software tool for makingannotated plasmid maps. It also sequencesediting, virtual digestions, and analysis ofsequences. DNA for Windows: is a compactand easy to use DNA analysis program, idealfor small scale sequencing projects. AnnHyb -(www.annhyb.free.fr) is a comprehensive DNAanalysis and edit tool which allows sequenceretrieving directly form the server, sequenceediting with proof reading, restriction analysis,translation etc. Another software that isavailable free of cost on the net for theidentification of restriction sites for variousrestriction enzymes in the given genomicsequence is called as WEBCUTTER 2.0 -(www.f irstmarket.com/cutter/cut2.html) .COPE - is an environment on pedigreemanagement and drawing. This environmentis intended as a facility for epidemiologistsand statisticians to share their familial datathrough the networks.www.bimas.dcrt.nih.gov/sw.html - Thiswebsite also houses a lot of molecular biologysoftwares used for various purposes.Comprehensive Genomic Sequence AnalysisPackages: These are a growing set of programsfor manipulating and analyzing “genetic” data.Linkage Analysis Tools - These programs areused to analyze pedigrees for linkage betweena diseased trait and a number of marker locifrom BIMAS. Linkage analysis software usedin gene mapping work is available at“linkage.rockefeller.edu”. Primer Selection ToolsThis is a computer program developed to aidin selecting oligonucleotide primers for DNA

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sequencing and for the polymerase chainreaction. The www.bioinformatics.org givesinformation on the latest developments inbioinformatics. The bioinfo.weizmann.ac.il/:From this site information is obtained onbioinformatics and computational biology. Itis basically an educational website, whichgives details on sequence analysis. Thewww.isb-sib.ch/: this is the Swiss Instituteof Bioinformatics, which educates onbioinformatics and has the state of artfacilities for this purpose. DNA software isalso available on bioinformatics atwww.sibc.ac.cn.

This study gives an insight on humangenome databases available on the net.

Various search engines were used to identifydifferent DNA databases. One hundred andsix databases giving information on variousaspects of human genetics were collected andclassified. Twenty software programs, whichwill be useful in molecular biology research,were found and these can be downloaded freeof cost. These databases and the softwareprograms can be used in any laboratoryoriented towards human genome research.

Reference:

1. McKusick VA. Mendelian Inheritance in Man.Tenth edition, The Johns HopkinsUniversity Press, Baltimore, 1992. Vol 1and 2.

Editor : Dr. Mahesh P Shanmugam 112

For Private Circulation Only

(contd. on page 108)

Last Page

Databases and free softwares on the Netfor DNA analysesVedam Lakshmi Ramprasad, Pradeep George Paul, Sarangapani Sripriya andGovindasamy Kumaramanickavel

entails coping with the distribution of dataamong these databases, the heterogeneity ofthe systems underlying these databases, andthe semantic (schema representation)heterogeneity of these databases. Earlyattempts to manage heterogeneous databaseswere based on revolving heterogeneity byconsolidating these databases eitherphysically, through integration into a singlehomogenous database, or virtually, byimposing a common definition language, datamodel, or even data base management system(DBMS), upon heterogeneous databases. Theseattempts failed because they required a verydifficult to attain degree of cooperation and acostly replacement of applications that werealready based on existing databases. The mosteffective way of coping with heterogeneousdatabases is to allow them to preserve theirautonomy, that is, their local definitions,applications, and policy of exchanging datawith other databases.

Approaches to managing heterogeneousdatabases include connecting them using theWorld Wide Web (WWW), organizing them intodatabase federations or multi databasesystems, and constructing warehouses. TheWorld Wide Web is officially described as a“wide area hypermedia information retrievalinitiative aiming to give universal access to alarge universe of documents”. The World WideWeb uses the Internet to transmit hypermediadocuments between computer usersinternationally. Heterogeneous databases canbe connected via WWW hypertext links at thelevel of individual data items. Data retrievalin such systems is limited to selecting astarting data item within one database andthen following hyperlinks between data items

Introduction:

Human genetics is the study ofinheritance in Man. Genetic disorderscompared to heart or lung diseases are rarein a population, but when 10,000 differentsingle gene disorders 1 and various othercomplex or multifactorial diseases are puttogether, they form a major group in healthand disease. Genetic studies have helped toidentify the genes responsible for deadlydiseases like breast cancer, retinoblastoma,Alzheimer’s, Huntington, Duchenne Musculardystrophy etc. The gene discovery is openingthe doors for prevention and bettermanagement of genetic diseases. The field ofgenetics is complex, rapidly growing and adeluge of new information is gained every day.The amount of information to be studied iscolossal. The field of human moleculargenetics is relatively new but what we knownow has been gathered over the last 30 years.The massive data that is generated in the fieldis not only stored efficiently but also isavailable in the public domain for free accessand retrieval.

A database is a data repository thatprovides a centralized and homogenous viewof data for multiple applications. The data ina database are structured according to adatabase definition, called schema, specifiedin a data definition language and aremanipulated using operations specified in adata manipulation language. Data definitionand manipulation languages are based on adata model that defines the semantics of theconstructs and operations supported by theselanguages. Comprehensive studies onmolecular biology data often involve exploringmultiple molecular biology databases, which