Central serous chorioretinopathy (CSC) is characterized by accumulation of fluid under the neurosensory retina and/or retinal pigment epithelium (RPE), resulting in a circumscribed area of serous retinal detachment (RD) that often involves the posterior pole. CSC has a male preponderance and generally affects the age group of 25–50 years. Visual acuity in these patients usually depends on the involvement of central macula and may be improved with a small hyperopic correction. Exposure to increased levels of endogenous or exogenous glucocorticoid is a well-established cause of CSC. Increased catecholamine levels leading to hyperpermeability of choroidal vasculature has been attributed to the development of CSC. CSC is relatively rare, but becomes a vision-threatening complication in patients with uveitis. In majority of the cases, the development of CSC in patients with uveitis can be attributed to corticosteroids, which remains the mainstay of management in uveitis. Also, it is of paramount importance to differentiate CSC from other uveitic entities that may present with subretinal fluid and mimic CSC. As the management of these conditions is paradoxical, initiation of corticosteroids in CSC can further aggravate and deteriorate the disease process. Development of concurrent CSC in patients of uveitis who are in need of acute immunomodulation can pose serious therapeutic challenge. Barring some of the case series, there is a scarcity of literature on CSC in patients with uveitis and we seek to investigate the demographic profile, treatment, and visual outcomes in patients of uveitis developing CSC in a tertiary eye care center in India.
This was a hospital-based retrospective case series that reviewed the files of all consecutive patients with uveitis, who developed CSC and presented at a tertiary center between June 1994 and May 2014 with a minimum follow-up of 6 months. Institute Ethics Committee approval was obtained, and the study adhered to the tenets of the Declaration of Helsinki.
All patients underwent a complete ophthalmic examination, including best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, tonometry, and posterior segment examination. Fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) were performed in all patients. Indocyanine green angiography (ICGA) and ultrasonography (USG) B-scan were done when indicated. In all patients, uveitis was diagnosed, categorized, and graded according to the Standardization of Uveitis Nomenclature Working Group criteria. Laboratory investigations, including complete blood count, sedimentation rate, angiotensin converting enzyme, serum lysozyme, tuberculin skin test, venereal disease research laboratory test, and chest X-ray were conducted on all patients and further relevant investigations were added based on the uveitic entities. The diagnosis of CSC was made by dilated fundus examination, combination of imaging of the retina and choroid with FFA, OCT, ICGA, or combinations of these imaging techniques. Subretinal fluid pocket or exudative RD is confirmed on clinical examination – both by slit lamp biomicroscopy and indirect ophthalmoscopy. Neurosensory detachment or pigment epithelial detachments in OCT, multiple leaks, typical ink blot, and/or smoke stack appearance in FFA were considered as diagnostic clues for CSC.
All patients were evaluated by an internist and additional consultations were sought with a rheumatologist, or a pulmonologist whenever deemed necessary. The data, including sex, age, clinical presentation, disease course and outcome, ocular involvement, types of uveitis, and associated systemic findings, were entered into a computer database. Furthermore, details of medications used for treating inflammation were recorded.
Data entry was done in Microsoft Office Excel worksheet. Statistical analysis was performed using SPSS Statistics, version 20.0 (International Business Machine Corp., USA). Patients’ BCVA were transferred from their records to LogMAR scale for the statistical analysis. Values of numerical characteristics were tested for normality and are presented as mean value (±SD), if normally distributed. The two-tailed paired t-test was used for statistical analysis to assess the improvement in BCVA. A P value <0.05 was considered significant.
A total of 22,721 patients of uveitis were seen in our hospital between June 1994 and May 2014. Search of our database revealed that 29 patients of uveitis developed CSC in this time period. Three patients were excluded from the study because of insufficient documentation and inadequate follow-up. The remaining 31 eyes of 26 patients were included in our study [Table 1]. Mean age of presentation of the patients in the current study was 42.8 ± 9.2 years (range: 29–70 years). Twenty-three (88.4%) of them were males and three (11.5%) were females. Out of 26, five patients (19.2%) developed CSC in both eyes. In 10 patients (38.4%) with uveitis, an infectious etiology could be detected. CSC was unilateral in all of the patients of uveitis with infectious etiologies. The causes of infectious and noninfectious uveitis in the current study are listed in Table 2.
In the current study, 23 patients (88.5%) were on oral steroids when they had developed CSC. Two eyes of two patients had received periocular corticosteroid injections before the development of CSC; one of them was on additional oral corticosteroid. One patient was on oral azathioprine (50 mg, twice a day), but had completed a course of oral steroids only 2 days before the onset of CSC. CSC developed in a patient of human leukocyte antigen (HLA)-B27-associated acute anterior uveitis, who was receiving topical corticosteroid and cycloplegic for the treatment of anterior chamber inflammation and was not on any form of systemic corticosteroids. Choroiditis (15 eyes, 48.4%) was the most common cause of uveitis in the present study [Fig. 1], followed by retinal vasculitis (4 eyes, 12.9%). Anterior uveitis, toxoplasma chorioretinitis, scleritis, and Vogt-Koyanagi-Harada (VKH) disease were seen in two eyes (6.4%) each. Fifteen eyes (48.4%) had active ongoing inflammation when a diagnosis of CSC was made.
The presence of subretinal fluid and sudden onset diminution of vision were the clinical clues that arose suspicion to CSC in majority of the cases and in six eyes (19.4%) presented with bullous serous RD. All those patients with bullous RD were on high-dose corticosteroid (>60 mg/day). Two of them were treated initially by increasing the existing dosage of corticosteroid elsewhere in the fear of flaring up of intraocular inflammation and they were on 60 mg/day dose. CSC with subretinal deposition of fibrin-like material was observed in seven (22.6%) eyes. Multiple RPE detachment was noted in six (19.3%) eyes. Multiple points of leakage of the dye in FFA were observed in 12 eyes (38.7%). Among the 12 eyes that showed multiple leaks in FFA, 10 eyes (83.3%) had choroiditis.
Causes of uveitis in the present study are highlighted in Table 2. In patients with uveitis because of infectious etiology, antimicrobial therapy was continued and systemic corticosteroid was stopped. Six patients were treated with anti-tubercular treatment (ATT). Of the 16 patients with noninfectious uveitis, six patients were switched over to immunosuppressives and in three patients, immunosuppressives were added considering the risk of recurrent inflammation. In nine eyes (29%), leakage of the dye was noted outside fovea and were treated with focal laser to the leak. One eye was treated with photodynamic therapy. Three eyes had more than one attack of CSC. Resolution of CSC was confirmed by clinical examination as well as with OCT. Mean time for resolution of CSC in the current study was 99 ± 61 days. Time taken for resolution of CSC in patients with infectious etiology (89.9 ± 89.1 days) was relatively less than that in patients with noninfectious etiology (115.1 ± 60.1 days).
Improvement of BCVA was noted in 22 eyes (70.9%). In three eyes (9.6%) vision remained the same even after the resolution of CSC, which can be attributed to the scar involving macula owing to choroiditis. Deterioration of vision was observed in six eyes (19.3%). Of these six eyes, four eyes had scar involving macula, and in two eyes subretinal fibrosis was noted. BCVA of the patients at the time of presentation with CSC was 0.56 ± 0.34 and BCVA after the resolution of CSC was 0.48 ± 0.5. There was statistically significant improvement in vision in these patients overall (paired t-test; P < 0.0005). No significant difference was found in BCVA improvement between patients with infectious and noninfectious uveitis (paired t-test; P < 0.31).
The association of CSC with corticosteroid therapy is well known and has been described by various authors. Although the exact cause of corticosteroid-induced CSC remains unclear, the corticosteroid-induced increased level of catecholamine and choroidal vascular hyperpermeability are believed to play a major role. CSC following exogenous administration of corticosteroid through topical, inhalational, systemic, local injections has been described in the literature. There is considerable variation in clinical presentation of CSC. CSC with bullous RD can mimic other causes of exudative RD secondary to inflammation and can be misdiagnosed. Treatment with corticosteroid in these patients can further aggravate the condition and can lead to severe loss of vision. In a case series by Papadia et al., 15 patients of CSC were misdiagnosed as posterior uveitis and three of them were treated with oral steroids.
Corticosteroid remains the mainstay of therapy in uveitis and patients with uveitis receiving corticosteroid are at risk to develop this vision-robbing complication. Also, the breakdown of blood-retinal barrier and disturbance in choroidal circulation due to inflammation may play a major role in the development of CSC in these patients. It is of utmost importance to identify CSC in uveitis patients and differentiate them from intraocular inflammation. Many case reports and few case series have described the association of CSC with patients receiving corticosteroid during the treatment of uveitis. The largest series on CSC in uveitis patients published to-date is by Papadia et al. and included 20 eyes of 14 patients. As the majority of the cases of uveitis with CSC are related to corticosteroid use, it is important to assess the role of other associated confounding factors in these patients.
Prevalence of CSC in patients with uveitis was 0.12%. Mean age of the patients in our study was 42.8 years, which is relatively higher compared to the study by Papadia et al. (34.8 years). Involvement of relatively older age group with corticosteroid-induced CSC has been reported previously in the literature. However, our finding is in accordance with a population-based, case-controlled study from Taiwan, which studied the association between topical ophthalmic corticosteroid and CSC (42.2 years). Bilateral CSC has been reported to be relatively more common in patients with corticosteroid-induced CSC. In our study 19.2% patients had developed bilateral CSC. In a similar study on uveitis patients with CSC by Papadia et al., bilateral CSC was observed in 42.8% of the uveitic patients. Relative lower number of bilateral CSC can be attributed to the fact that 38.4% of our patients had an infectious etiology and we did not observe any case of bilateral CSC in this group. Patients with uveitis due to infectious etiology were treated with suboptimal dose of corticosteroids (0.5 mg/kg body weight) which may explain the lower incidence of bilateral CSC in these patients. Papadia et al. had only two cases (14.2%) of ocular toxoplasmosis as infectious etiology, and in majority of their patients the underlying uveitic entity was Behçet's uveitis (64.3%), which often requires aggressive therapy with immunosuppressives, including systemic corticosteroid. In our study, 88.5% of the patients were on oral corticosteroid, which is in accordance with the study by Papadia et al.
Topical ophthalmic medications after instillation can be absorbed into the systemic circulation via conjunctival vessels or nasolacrimal duct. In a population-based study by Chang et al., history of topical ophthalmic corticosteroid use was present in 1373 (47%) patients with CSC. In the current study, a 41-year-old patient with HLA-B27-related uveitis developed CSC following topical use of corticosteroid (1% prednisolone acetate ophthalmic suspension). The other three patients in our study were on topical steroid in addition to oral steroid, making it difficult to comment on the role of topical ophthalmic corticosteroid in the development of CSC in these patients. Similarly, CSC following regional injection of corticosteroid is not rare. Baumal et al. reported a case of HLA-B27-associated iritis, who developed CSC following periocular steroid. In the current study, two eyes with CSC had received periocular steroid injections and one of them was on additional oral corticosteroid.
One of the important observations in this study was that 48.4% of the patients had choroiditis as the underlying cause of uveitis. A relative higher association of CSC in choroiditis patients in our cohort may be due to marked destabilization of blood ocular barrier in these eyes, making them more vulnerable to develop CSC. This is further supported by another finding in the current study where 83.2% of the patients with multifocal leak in FFA presented choroiditis.
Discrimination between reactivation of the inflammation in Vogt–Koyanagi–Harada syndrome and bullous RD due to CSC can be challenging. Six (19.4%) of our patients in the current study had presented with bullous RD. Two of them were treated initially by increasing the current dosage of corticosteroid elsewhere in fear of flaring up of intraocular inflammation. Three of these six patients required additional management in the form of laser to the leaks apart from discontinuation of oral corticosteroid. In a case series of seven patients with bullous RD due to CSC by Kunavisarut et al., three patients were misdiagnosed as Vogt–Koyanagi–Harada syndrome and were treated with high-dose corticosteroid, which aggravated their ocular symptoms.
The current study included 10 eyes (32.2%) of patients with uveitis due to infectious etiology. Six of them had tuberculosis as primary etiology and was treated with ATT. We did not find any statistically significant improvement in BCVA following resolution of CSC in patients with uveitis due to infectious etiology (P > 0.361) when compared with the cohort of patients with noninfectious entities. This can be attributed to the relatively small number of patients with infectious uveitis or due to collateral damage to the ocular tissue caused by the infectious etiology. However, in contrast to the cohort with noninfectious etiology, which included 21 eyes (67.7%) of the 16 patients, mean duration of resolution of CSC in cohort with infectious etiology patients was relatively less (89.9 ± 89.1 days). Relatively lower duration of resolution of CSC in our cohort with infectious uveitis patients may also have been affected by the six patients of tuberculosis, who were on ATT, including rifampicin. Rifampicin, an enzymatic activator known to enhance the corticosteroid metabolism, may play a role in relatively early resolution of CSC following discontinuation of oral corticosteroid among the patients taking ATT.
One limitation of our research was the sample size. Clearly 31 eyes of 26 patients are not enough to make generalization about development of CSC in uveitis patients. However, to the best of our knowledge, the present study represents the largest case series on CSC in uveitic patients. Being a retrospective analysis, we could not assess the other confounding factors, such as emotional stress, personality assessment, presence or absence of endogenous hypercortisolism in uveitis patients in our study. Nonetheless, we believe that a clear pattern of CSC in patients with uveitis has emerged out of our study.
Diagnosis and management of CSC in patients of uveitis remain challenging. Patients with higher dose of systemic steroids tend to develop bullous RD, whereas those with suboptimal dose, the relative risk is lesser. Patients with choroiditis are more prone to develop CSC compared with other subsets of uveitis. Alternative treatment modalities, such as focal laser and initiation of immunomodulatory therapy, may be considered earlier in such noninfective uveitic patients with co-existing CSC to prevent vision loss caused by both entities.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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