Volume 17 Number 6 / December 2013 Baldwin, Risma, and Longmuir 629

The excellent visual and systemic outcome in our pa-tient is unexpected based on the natural history ofS. prolificans septicemia. The successful eradication ofS. prolificans may be attributed to the combination ofintensive systemic triple antifungal therapy, weekly in-travitreal voriconazole injections (17 over 4 months)and neutrophil count recovery aided by G-CSF. Itmay also be attributed to the fortunate macular sparingand close follow-up during the course of active endop-thalmitis. Thus far, all reported cases of S. prolificans en-dophthalmitis have required enucleation6-8 or ended inpatient death.1,9,10 To our knowledge, this is the firstcase of successfully treated endogenous S. prolificansendophthalmitis. Our patient’s recovery providesencouraging evidence that control of S. prolificanssepticemia in immunocompromised patients is possiblewith aggressive treatment.

Literature Search

The PubMed database was searched, without languageor date restrictions, using the following terms: (scedosporium[MeSH Terms] OR scedosporium [All Fields]) AND(miltefosine [Supplementary Concept] OR miltefosine [AllFields]). Manual search of the reference lists of relevantpublications was also performed; however, no furtherarticles were found.

Author affiliations: aSchool of Medicine and bDepartment of Ophthalmology, University ofIowa Hospitals and Clinics, Iowa City, IowaSubmitted May 9, 2013.Revision accepted July 8, 2013.Published online November 7, 2013.Correspondence: Susannah Longmuir, MD, University of Iowa, 200 Hawkins Drive,

Iowa City, IA 52246 (email: susannah-longmuir@uiowa.edu).J AAPOS 2013;17:629-631.Copyright � 2013 by the American Association for Pediatric Ophthalmology and

Strabismus.1091-8531/$36.00http://dx.doi.org/10.1016/j.jaapos.2013.07.011

Journal of AAPOS

References

1. Maertens J, Lagrou K, Deweerdt H, et al. Disseminated infectionby Scedosporium prolificans: an emerging fatality among haematologypatients: case report and review. Ann Hematol 2000;79:340-44.

2. Kesson AM, Bellemore MC, O’Mara TJ, Ellis DH, Sorrell TC.Scedosporium prolificans osteomyelitis in an immunocompetent childtreated with a novel agent, hexadecylphospocholine (miltefosine), incombination with terbinafine and voriconazole: a case report. ClinInfect Dis 2009;48:1257-61.

3. Meletiadis J,Mouton JW,Meis JF, Verweij PE. Combination chemo-therapy for the treatment of invasive infections by Scedosporium pro-lificans. Clin Microbiol Infect 2000;6:336-7.

4. Sundar S, Olliaro PL. Miltefosine in the treatment of leishmaniasis:clinical evidence for informed clinical risk management. Ther ClinRisk Manag 2007;3:733-40.

5. Stevens DA, Brummer E, Clemons KV. Interferon-gamma as an anti-fungal. J Infect Dis 2006;194(Suppl 1):S33-7.

6. Taylor A, Wiffen SJ, Kennedy CJ. Post-traumatic Scedosporium in-flatum endophthalmitis. Clin Experiment Ophthalmol 2002;30:47-8.

7. Wood GM, McCormack JG, Muir DB, et al. Clinical features ofhuman infection with Scedosporium inflatum. Clin Infect Dis 1992;14:1027-33.

8. Marin J, SanzMA, Sanz GF, et al. Disseminated Scedosporium inflatuminfection in a patient with acute myeloblastic leukemia. Eur J ClinMicrobiol Infect Dis 1991;10:759-61.

9. McKelvie PA, Wong EY, Chow LP, Hall AJ. Scedosporium endoph-thalmitis: two fatal disseminated cases of Scedosporium infection pre-senting with endophthalmitis. Clin Experiment Ophthalmol 2001;29:330-34.

10. Vagefi MR, Kim ET, Alvarado RG, Duncan JL, Howes EL,Crawford JB. Bilateral endogenous Scedosporium prolificans endoph-thalmitis after lung transplantation. Am J Ophthalmol 2005;139:370-73.

Transient leopard spot corneal endothelial stainingwith trypan blue during cataract surgery in a childwith congenital rubella syndromeAndrew Baldwin, BS,a Justin Risma, MD,b and Susannah Longmuir, MDb

We report the complication of corneal endothelial staining with try-pan blue that limited the surgical view during cataract extraction in

a 10-month-old boy. The boy had presented with a pigmentary reti-nopathy, microphthalmia, and a dense, white, unilateral congenitalcataract. He was suspected of having, and was later diagnosed with,congenital rubella syndrome.We hypothesize that the corneal stain-ing may have resulted from virally induced corneal endothelialdamage. To our knowledge, this is the first reported case of trypanblue adversely affecting congenital cataract surgery.

Case Report

A10-month-old Vietnamese boy was referred tothe University of Iowa Hospitals and Clinics Pe-diatrics Service for evaluation of microphthalmia,

FIG 1. Intraoperative photograph of left eye through the operating mi-croscope with evident circular pattern of staining following injection ofTrypan blue.

FIG 2. Dilated color fundus photographs of the right eye (A) taken attime of cataract surgery and of the left eye (B) taken at an examinationunder anesthesia 2 months after surgery. Note presence ofperipapillary pigmentary changes and salt-and-pepper pigmentaryretinopathy.

630 Baldwin, Risma, and Longmuir Volume 17 Number 6 / December 2013

unilateral congenital cataract, and retinopathy. He wasborn in Vietnam at full term after an unremarkable preg-nancy. Past medical history was significant for an un-known heart procedure performed in Vietnam,microcephaly, hypospadias, left-sided cryptorchidism,and failure to thrive. Family history was negative for cat-aracts. His father had noted a white-appearing pupil and asmall-appearing left eye since birth. There was no historyof known infections, fevers, or rashes in either the patientor the patient’s mother during pregnancy. The patienthad never received the measles, mumps, and rubella vacci-nation.

On ophthalmological examination, visual acuity byfixation preference was central, nystagmoid, and main-tained in the right eye and eccentric, nystagmoid, andunmaintained in the left eye. A fine-amplitude horizon-tal pendular nystagmus was present in both eyes. A largevariable esotropia was present in the left eye. There wasno relative afferent pupillary defect. The anteriorsegment of the right eye was normal, including a hori-zontal corneal diameter of 10.5 mm. Anterior segmentexamination of the left eye was significant for a horizon-tal corneal diameter of 8.25 mm and a dense white nu-clear cataract. Examination of the posterior segmentrevealed a cup/disk ratio of 0.1 in the right eye and“salt-and-pepper” pigmentary changes in the retina(Figure 1) of the right eye. There was no view of thefundus in the left eye. We suspected a perinatal infec-tion as the cause of his ocular, cardiac, and urologicfindings, and the patient was provisionally diagnosedwith congenital rubella syndrome (CRS); the parentselected to defer laboratory testing until after cataractsurgery.

The patient underwent lensectomy with anterior vitrec-tomy of the left eye. Immediately after induction of anes-

thesia, intraocular pressure as measured by Tono-PenXL (Reichert Technololgies, Depew, NY) was 7 mm Hgin the right eye and 18 mm Hg in the left eye. Centralcorneal thickness as measured by corneal pachymetry was531 mm in the right eye and 630 mm in the left eye. A-scan echography by immersion revealed axial eye lengthsof 20.0 mm on the right and 18.0 mm on the left. Duringsurgery, trypan blue was used to assist with visualizationof the anterior capsule. Despite copious irrigation, the try-pan blue stained the corneal endothelium in a sporadic,leopard spot–like pattern (Figure 2). The staining persistedand partially impaired the surgical view. We proceededcarefully and switched to a vitrectorrhexis, followed by len-sectomy, posterior capsulotomy, and planned anterior

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Volume 17 Number 6 / December 2013 Baldwin, Risma, and Longmuir 631

vitrectomy, which were completed successfully. The pa-tient was left aphakic and fitted for a contact lens. Thecorneal endothelial staining, as well as some transientcorneal clouding, resolved over the next several weeks.Blood work returned positive for anti-rubella immuno-globulin G, confirming the diagnosis of (CRS).

Discussion

CRS is an acquired disorder, rarely encountered indeveloped countries, with ocular and systemic manifes-tations. Among the most common ocular findings in pa-tients with CRS is visually significant monocularcataract.1 Although the visual prognosis of childrenwith CRS cataracts is poor,2 early surgical extractionis generally agreed to offer the best visual outcomes.3

The ideal timing for surgical removal of visually signif-icant congenital cataracts is from 4 to 6 weeks of age tominimize the surgical complications sometimes associ-ated with early surgery and the increased risk of ambly-opia associated with late surgery.3-4 Lensectomy withanterior vitrectomy is a common surgical approach inCRS patients,3 and trypan blue is commonly adminis-tered intracamerally during cataract surgery to aid invisualization of the anterior lens capsule for capsulo-rhexis, especially with dense, white cataracts thatcompromise the red fundus reflex.5

We used trypan blue intraoperatively to obtainoptimal visualization.6 Unfortunately, its use was disad-vantageous in the present case because the staining ofthe corneal endothelium compromised the surgicalview. We hypothesize the corneal staining may have re-sulted from virally induced corneal endothelial damage.To our knowledge, this case is the first to documentstaining of the corneal endothelium by trypan blue dur-ing cataract extraction. One of the ophthalmologic se-qulae of CRS with documented endothelial damage ispersistent corneal edema independent of congenitalglaucoma.7 In 1983 Deluise and colleagues7 reportedthat histologic examination of a 36-week-old CRS pa-tient with persistent corneal edema revealed disruptionof Descemet’s membrane, corneal endothelial derange-ment and loss, corneal stromal swelling, and deep inter-stitial keratitis, postulating that these findings were dueto viral infiltration of the endothelium with subsequentinflammation and damage. Rubella virus–induced

Journal of AAPOS

cellular damage, such as that experienced in persistentcorneal edema, would make the affected endothelialcells susceptible to staining with trypan blue. Trypanblue staining of corneal endothelial cells with disruptedouter cell membranes has been documented: it has beenused to test for cellular integrity and viability in humandonor corneas.8 Although our patient did not exhibitsigns of persistent corneal edema, we hypothesize thatthe leopard spot pattern observed in our case was dueto trypan blue staining of corneal endothelial cells thathad been damaged by the rubella virus. The virally in-fected endothelial cells may have lost integrity of theirouter cellular membrane and facilitated their stainingwith trypan blue.

Literature Search

PubMed (English-language articles only) and Web of Sci-ence were searched, most recently on May 2, 2013, usingthe following terms: trypan blue, congenital rubella syndrome,and unilateral congenital cataract. Articles in reference lists ofselected reports were also searched.

References

1. Wolff SM. The ocular manifestations of congenital rubella. Trans AmOphthalmol Soc 1972;70:577-614.

2. Vijayalakshmi P, Srivastava KK, Poornima B, Nirmalan P. Visualoutcome of cataract surgery in children with congenital rubella syn-drome. J AAPOS 2003;7:91-5.

3. Birch EE, Stager DR. The critical period for surgical treatment ofdense congenital unilateral cataract. Invest Ophthalmol Vis Sci1996;371532-8.

4. Vishwanath M, Cheong-Leen R, Taylor D, Russell-Eggitt I, Rahi J. Isearly surgery for congenital cataract a risk factor for glaucoma? Br JOphthalmol 2004;88:905-10.

5. Melles GR, deWaard PW, Pameyer JH,Houdijn BeekhuisW.Trypanblue capsule staining to visualize the capsulorhexis in cataract surgery. JCataract Refract Surg 1999;25:7-9.

6. Saini JS, Jain AK, Sukhija J, Gupta P, Saroha V. Anterior and posteriorcapsulorhexis in pediatric cataract surgery with or without trypan bluedye: randomized prospective clinical study. J Cataract Refract Surg2003;29:1733-7.

7. Deluise VP, Cobo LM, Chandler D. Persistent corneal edemain the congenital rubella syndrome. Ophthalmology 1983;90:835-9.

8. Sperling S. Evaluation of the endothelium of human donor corneas byinduced dilation of intercellular spaces and trypan blue. Graefes ArchClin Exp Ophthalmol 1986;224:428-34.