PERSISTENT CENTRAL SEROUS CHORIORETINOPATHY SECONDARY TO CHRONIC CORTICOSTEROID TREATMENT FOR AUTOIMMUNE HEPATITIS

AMANDA S LEGGE

ABSTRACTCASE REPORT: A sixty one-year-old Hispanic male has been experiencing episodes of blurred vision O.U. for approximately eleven years. He was diagnosed with chronic central serous chorioretinopathy shortly after beginning steroid treatment for autoimmune hepatitis twelve years ago. Since that time the posterior pole of both eyes has undergone severe retinal pigment epithelium atrophy and subsequent permanent deterioration of vision in the right eye. Although subretinal fluid was still present in both eyes, his vision was stable with minimal active leakage. Treatment options were discussed; however intervention at this time was deferred. The patient continues to be monitored closely at four month intervals.DISCUSSION: Central serous chorioretinopathy is an idiopathic disorder in which a serous detachment of the retina or retinal pigmented epithelium occurs by means of fluid diffusing from the choriocapillaris through Bruch’s membrane. Often the condition is self-resolving and treatment is unnecessary. However, in the chronic form, laser photocoagulation or medical intervention is needed to reduce the risk of permanent visual impairment. Several treatment options are available. Each patient must be evaluated to determine which treatment, if any, will be of maximum benefit with minimal risk.

Central serous chorioretinopathy (CSCR) is a fairly common, idiopathic, disorder of the choroid. More specifically it is a disorder of the choriocapillaris and Bruch’s membrane. Fluid from the choriocapillaris diffuses through Bruch’s membrane resulting in a serous detachment of the sensory retina or retinal pigment epithelium (RPE). This causes a blurring or distortion of central vision which often resolves without intervention. Chronically, CSCR can result in a dysfunctional RPE and concomitant visual reduction1.

The following case report illustrates the effects of persistent CSCR secondary to steroid treatment for autoimmune hepatitis as well as treatment considerations.

CASE REPORT

HISTORY

The patient is a 61-year-old Hispanic male. His medical history is remarkable for Raynaud’s syndrome, hypothyroidism, hyperlipidemia,

scleroderma, hypertension, and autoimmune hepatitis. His most current medications included ranitidine, omneprazole, amlopidine, levothyroxine, acetaminophen, azathioprine, and prednisone. He reported allergies to adhesive tape and rayon.

He was first diagnosed with autoimmune hepatitis 12 years ago and began a regimen of long term steroid treatment with prednisone. The dosage varied based on the patient symptoms and serum tests including AST, ALT, alkaline phosphatase, IgG, and bilirubin. The patient is currently medicated with 20 mg prednisone per day for the last 8 months. In the past this ranged from 0 mg to 50 mg per day. He has also been on a constant dose of azathioprine 200 mg per day for the last 5 years to control hepatitis signs and symptoms.

The patient’s ocular history is remarkable for chronic central serous chorioretinopathy (CSCR) O.U. which CSCR became relapsing and remitting approximately 6 months after beginning steroid treatment. At initiation of

treatment he was given a high dosage of oral prednisone but was unable to recall the exact quantity. He reported that he had fluctuating vision in both eyes for the next few years. The right eye worsened permanently approximately 9 years ago.

The patient also reported having an episode of posterior uveitis O.S. more than 15 years ago that resolved uneventfully without treatment.

The chief complaint upon presentation was moderate fluctuating vision O.S. and difficulty adapting from light to dark environments. He felt that the vision in his left eye improved from 6 months ago when his visual acuity was measured 20/40.

DIAGNOSTIC DATA

The patient’s aided visual acuity was count fingers at 3 feet O.D. and 20/25 O.S. without pinhole improvement O.U. Pupils were round, equal, and reactive to light with no relative afferent defect. Extraocular motility testing found no restrictions of muscle movement.

Confrontation visual fields were full to finger counting O.D., O.S.

Intraocular pressures measured 14 mmHg O.D., O.S. Anterior segment evaluation was unremarkable O.U.

Amsler grid revealed a significant superior nasal scotoma O.D. The patient reported that this has been stable for many years. The left eye showed mild central metamorphopsia only. Humphrey 24-2 visual field showed the same superior nasal scotoma O.D. and was within normal limits O.S.

Posterior segment examination of the right eye revealed a shallow 1.5 disc diameter serous detachment inferior to the macula along with several areas of pigmented atrophy. Pigment changes associated with guttering was found along the inferior arcade. The left eye showed minimal foveal fluid, although a small retinal pigment epithelium (RPE) detachment was seen in the papillomacular bundle and a small area of subretinal fluid was seen just temporal to the foveal avascular zone. (figure 1)

Figure 1. Fundus Photography illustrating tracts of retinal and RPE disturbance and minimal subretinal fluid O.U.

Optical coherence tomography was performed Inferior, diffuse, intraretinal thickening O.D. was seen. The left eye showed a small RPE

detachment and an area of subretinal fluid in the papillomacular bundle was noted. This coincided with the fundus findings. (figure 2)

O.D. O.S.

Figure 2. Optical Coherence Tomography illustrating the diffusemacular thickening O.D. and both subretinal fluid and a small RPE detachment O.S.

Fundus autofluorescence (FAF) photography showed the extent of the RPE atrophy O.U. The more recent descending tracts of RPE atrophy are hypoautofluorescent surrounded by an area of hyperautofluorescence most obvious inferiorly O.D. This indicates recent leakage and

subsequent RPE damage that has migrated inferiorly. Discrete hyperautofluorescent granules were seen temporal to the macula O.S revealing evidence of a chronic serous detachment in that area. (figure 3)

Figure 3. Fundus Autofluorescence illustrating the extensive RPE alterations and minimal leakage O.U.

A fluorescein angiography was performed. Results showed mild, diffuse active leakage greater O.D. than O.S. Again, as with FAF, no pinpoint leakage was detected in either eye.

The right macula showed significant RPE window defects that accounts for his poor vision in that eye. (figure 4)

Figure 4. Early and late phase fluoroscein angiography illustrating minimal diffuse, activesubretinal leakage and RPE window defects O.D. greater than O.S.

DIAGNOSIS AND FOLLOW-UP

At this presentation the vision and subretinal fluid was stable in both eyes. Although the FAF photographs revealed mild subretinal fluid, the fluorescein angiography did not show any active leakage O.D., O.S. Because active leakage was not evident, he is currently not a candidate for thermal laser treatment.

Treatment options were discussed, including photodynamic therapy (PDT) and intravitreal injections.

At this time PDT was not advised because of his stable visual acuity O.U. and the potential for PDT to cause choroidal neovascularization or RPE atrophy.

Intravitreal injection of anti-vascular endothelial growth factor drugs, such as

Lucentis, was discussed. The patient was also educated on the lack of a definite positive correlation of anti-VEGF drugs reducing CSCR in current studies. The patient decided to defer treatment at present.

The patient was instructed to maintain careful 4 month follow ups. Any rapid changes in vision were to be reported so treatment options could be altered if necessary.

The patient understood that because of his ongoing steroid regimen his prognosis is guarded. The patient’s primary care physician was made aware of his chorioretinopathy and is cognizant of keeping the prednisone at the lowest possible therapeutic dosage.

The patient is wearing polycarbonate dress glasses full time for protection of his left eye. He is aware of the necessity to guard this eye because of his monocular status. He wears safety goggles for yard work and vehicle maintenance.

DISCUSSION

Central serous chorioretinopathy (CSCR) is an idiopathic disorder of the choroid and retina. The acute form is most common and often resolves spontaneously without intervention within 4 months2. Typical symptoms include micropsia, metamorphopsia, and decreased vision.

Chronic CSCR has the potential to cause diffuse retinal pigment epitheliopathy or choroidal neovascularization, either of which can cause a permanent decrease in vision1. Several treatment options are then considered to stop the recurrent leakage and prevent vision loss.

Although most cases are idiopathic, CSCR has a strong association with increased cortisol levels, whether endogenous or exogenous. Type A personality is a well recognized etiology of CSCR where increased endogenous cortisol levels are routinely measured2,3. Similarly patients treated with exogenous steroids, administered by any route, for autoimmune or inflammatory disorders are at risk for developing CSCR3,4.

The mechanism by which cortisol causes CSCR is minimally understood. Cortisol may be responsible for choroidal vascular spasm by inhibiting the parasympathetic nervous system and promoting the sympathetic nervous system. This spasm causes temporary damage to the choroid and results in leakage of serous fluid. The pressure created beneath Bruch’s membrane and the RPE disrupts the outer blood retinal barrier and allows the accumulation of fluid under the retina5. Permanent vision loss is thought to be caused by the persistent detachment of the photoreceptors to the RPE and source of nourishment6.

Studies show that CSCR typically resolves spontaneously once exogenous steroids are discontinued4. Unfortunately many patients cannot discontinue a steroid regimen because of a systemic inflammatory disease. Therefore careful monitoring and treatment considerations must be given to this complex population.

DIAGNOSTIC TECHNIQUES

Several techniques are used to diagnose and determine appropriate management of CSCR. These include biomicroscopy, optical coherence tomography (OCT), fluorescein angiography,

indocyanine green angiography, and fundus autofluorescence photography as well as visual field and Amsler grid testing.

Commonly biomicroscopy is all that is needed to diagnose CSCR because of its unique presentation. In active CSCR, a serous detachment of the retina is seen near the fovea, although it can rarely be eccentric near the vascular arcades. Retinal pigment epithelium (RPE) abnormalities are present once the fluid resolves. RPE hypopigmentation rather than atrophy is most common; however RPE atrophy is the cause of severe, permanent vision loss from CSCR7. Primary RPE hyperpigmentation is rare. Rather, the accumulation of subretinal fibrous deposits is reflected darkly during biomicroscopy1.

Other techniques are used to monitor the retinal status quantitatively over time. OCT can determine the amount of fluid and consequential thickness of the macula noninvasively and objectively. It is also used to monitor progression over time.

Retinal thickness during CSCR is a result of the buildup of serous fluid under the retina as well as subclinical edematous cells within retina8. The symptom of micropsia is thought to be caused by the intracytoplasmic swelling of the Müller cells which causes photoreceptor disruption9. OCT testing shows any serous retinal detachment as low reflectivity under the retinal layers or below the RPE in the case of an RPE detachment. Additionally, the detached retina itself often shows intraretinal areas of low reflectivity demonstrating the subclinical intraretinal swelling8.

Angiographic studies are useful to determine any active leakage sites and vascular changes.

The two most recognizable fluoroscein angiography (FA) leaks are the ink blot and smokestack patterns. A majority of CSCR leaks are characterized by leakage of fluid within the serous detachment zone without any typical pattern. FA typically shows a focal leak as an enlarging exudation of dye which can guide photocoagulation laser10.

Alternatively, indocyanine green angiography (ICGA) typically shows a more widespread exudation of dye from the choriocapillaris surrounding a focal leakage. This demonstrates that CSCR is foremost a choroidal disease11. Furthermore ICGA shows hypofluorescent areas not evident in FA in chronic CSCR. These are areas of RPE damage that are often subclinical during biomicroscopy or FA which illustrates the widespread damage that CSCR causes to subretinal structures12.

A noninvasive imaging technique for CSCR is fundus autofluorescence (FAF). The fluorescence is derived from lipofuscin, a yellow-brown aging pigment commonly found in the retina. Therefore it indirectly gives information about the metabolic activity of the RPE. Loss of photoreceptors results in decreased autofluorescence because the metabolic demand on the RPE is diminished. Focal increase in autofluorescence is due to increased turnover of the outer photoreceptor segments or an abnormality in the phagosomal uptake of lipofuscin from them13.

FAF in acute CSCR is consistent with a focal increase in autofluorescence over the serous retinal detachment. This is due to the abnormal degradation of phagosomal material from the

photoreceptor outer segments because of a sick RPE13,14.

In the chronic form, FAF shows mixed hyper- and hypoautofluorescence. The hypoautofluorescence in chronic CSCR corresponds with loss of photoreceptor outer segments with secondary reduction in RPE metabolic activity. The atrophy of this layer coincides with a reduction of vision, especially if present centrally15.

THERAPEUTIC CONSIDERATIONS

Treatment is considered if a serous detachment is persistent for several months, recurrence if any previous episode caused a sustained visual deficit, or if the patient requires faster restoration of vision2.

Thermal photocoagulation and photodynamic therapy (PDT) are currently the mainstay of CSCR treatment. Other possibilities are anti-vascular endothelial growth factor (anti-VEGF) injections, anti-glucocorticoid agents, oral acetazolamide, and adrenergic receptor inhibition1.

Photocoagulation has been used for decades in the treatment of CSCR. The application of thermal laser to the site of leakage resolves the serous fluid at a faster rate than no treatment. Resolving the detachment may prevent photoreceptor loss by shortening the length of time these cells are separated from the RPE, choriocapillaris, and proper nutrition17.

Thermal photocoagulation carries risks that are important to consider before proceeding with treatment. These include inadvertent foveal burns, pre- and subretinal fibrosis, choroidal

neovascularization, and progressive expansion of laser burns18.

A pinpoint, extrafoveal, leak must be seen on FA in order to proceed with this laser therapy. With candidacy, the goal of photocoagulation in CSCR is 200µm confluent spots in the area of leakage at an intensity to bleach without whitening the outer retina1,19. This limits the amount of damage to the choroid and reduces the risk of secondary choroidal neovascularization. Minimal laser treatment with maximal results is the objective.

Visudyne PDT is often utilized when photocoagulation is inappropriate. This includes sub- or juxtafoveal leakage sites or when a pinpoint site of leakage is not defined. PDT decreases subretinal fluid by selectively occluding vessels in the choriocapillaris. This occurs through cytotoxic damage of endothelial cells and consequential thrombosis20. Minimal retinal or choroidal damage occurs with this technique21.

Although overall less damaging to the RPE, choroid, and retina, PDT also has the potential to induce choroidal neovascularization. In addition it requires avoidance of sunlight after treatment for 24-36 hours because of photosensitization22. This must be weighed against the benefits when considering PDT treatment.

More recent studies are considering anti-VEGF agents for the treatment of CSCR. VEGF has profound effects on vascular hyperpermeability, which is the underlying reason for CSCR. These agents are thought to reduce subretinal fluid by decreasing the concentration of VEGF released by choroidal ischemia23.

These studies have not shown a highly positive link to reducing CSCR and improving vision long term24. Anti-VEGF injections come with low risk and have shown short term benefit to reducing leakage in CSCR in some studies. Thus it is a viable treatment option for CSCR when other methods are avoided.

Anti-glucocorticoid medications, such as mifepristone and ketoconazole, are an alternative currently being investigated for the treatment of CSCR25,26. Increased cortisol levels are well documented to cause CSCR. Anti-glucocorticoid agents aim to reduce cortisol levels thereby reducing serous detachments and improving visual acuity in patients. Both medications have mixed results according to recent studies26,27. More studies are warranted before they become standard treatment options.

Several other treatment methods have been proposed for CSCR including acetazolamide, adrenergic receptor inhibition, and beta

blockers28. Alternative medicines, such as acupuncture29, have also been studied. None have been shown to have a direct positive correlation with the long term reduction or preservation of vision from CSCR.

Chronic central serous chorioretinopathy is difficult to manage when caused by persistent steroid use that cannot be discontinued. Several options exist for the treatment of CSCR. The risk and benefit of all treatment strategies must be considered.

The patient in this case is currently best managed with observation because of his stable vision and the potential for tapering his prednisone dosage in the near future. Close monitoring along with proper patient education and primary care physician involvement is an appropriate treatment option at this time. Medical interventions will be discussed if the patient’s vision or retinal status decreases over time.

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