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Topic An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. Clinical relevance The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. Methods An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. Results Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis. Discussion Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence.

Topic The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). Clinical Relevance The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. Methods Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. Results Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. Discussion The COTS consensus guidelines were generated based on the evidence from published literature, specialists’ opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.

To investigate the association between Mooren's ulcer and intestinal hookworm infestation in South India.Prospective observational case-control study.Fifteen patients with Mooren's ulcer and 30 age- and gender-matched controls seen at Aravind Eye Hospital.Stool samples from the Mooren's ulcer patients and controls were collected and analyzed for presence of hookworm infestation.Prevalence of hookworm infestation in Mooren's ulcer patients and controls.There was a statistically significant correlation between intestinal hookworm infestation and the occurrence of Mooren's ulcer (P = 0.009). Retrospective exploratory subgroup analyses suggested that the correlation between intestinal hookworm infestation and the occurrence of Mooren's ulcer in men (P0.0001) was stronger than the correlation in women, with no statistically significant difference being observed in the prevalence of hookworm infestation between women with Mooren's ulcer and female control subjects (P0.99). Similarly, when both the Mooren's ulcer and the control subject groups were analyzed retrospectively by age50 years or age50, subjects with an age over 50 demonstrated a stronger correlation between hookworm infestation and Mooren's ulcer than controls (P = 0.017), whereas there was no statistically significant difference in the prevalence of hookworm infection between Mooren's ulcer subjects and control subjectsor = 50 (P = 0.31).Intestinal hookworm infestation appears to be associated with the development of Mooren's ulcer in South India. Although the power of our retrospective exploratory subgroup analyses was limited by multiple testing and small sample sizes, these data suggest further that the correlation between intestinal hookworm infestation and the development of Mooren's ulcer may be greatest in male patients with more advanced age.

Objective To study effects of intravitreal pegaptanib (Macugen) on retinal neovascularization. Design Retrospective analysis of a randomized clinical trial. PARTICIPANTS, INTERVENTION, AND MAIN OUTCOME MEASURES: Individuals with retinal neovascularization identified from a multicenter, randomized, controlled trial evaluating pegaptanib for treatment of diabetic macular edema, with a best-corrected visual acuity letter score between 68 and 25 (approximate Snellen equivalent between 20/50 and 20/320) and receiving a sham injection or intravitreal pegaptanib (0.3 mg, 1 mg, 3 mg) administered at study entry, week 6, and week 12, with additional injections and/or focal photocoagulation as needed during the ensuing 18 weeks, up to a maximum of 6 pegaptanib/sham therapies, were evaluated. Scatter panretinal photocoagulation before study enrollment was permitted, but not within 6 months of randomization and study entry. Changes in retinal neovascularization were assessed on fundus photographs and fluorescein angiograms graded at a reading center in a masked fashion. Results Of 172 participants, 19 had retinal neovascularization in the study eye at baseline. Excluding 1 who had scatter photocoagulation 13 days before randomization and 2 with no follow-up photographs, 1 of the remaining 16 subjects had panretinal photocoagulation during study follow-up. Of these 16 subjects, 8 of 13 (62%) in a pegaptanib treatment group (including the one receiving panretinal photocoagulation), 0 of 3 in the sham group, and 0 of 4 fellow (nonstudy) eyes showed either regression of neovascularization on fundus photographs or regression or absence of fluorescein leakage from neovascularization (or both) at 36 weeks. In 3 of 8 with regression, neovascularization progressed at week 52 after cessation of pegaptanib at week 30. Conclusions Most subjects with retinal neovascularization at baseline assigned to pegaptanib showed regression of neovascularization by week 36. These findings suggest a direct effect of pegaptanib upon retinal neovascularization in patients with diabetes mellitus.

Objective To describe subretinal fibrosis as a long-term complication of Vogt-Koyanagi-Harada (VKH) disease. Design Retrospective, clinic-based, cross-sectional study and clinical correlation. Participants Ten patients with VKH disease and subretinal fibrosis were seen at two uveitis referral centers between 1977 and 1997. Intervention A review of the historical, clinical, and fluorescein angiographic features was performed. Main outcome measures The prevalence, demographic and clinical features, and time to development of subretinal fibrosis were summarized. Results Subretinal fibrosis occurred in 20 eyes of 10 patients with VKH disease, an overall prevalence of 8% between the two institutions. Patient age ranged from 16 years to 48 years, with a median of 34.5 years. Five patients were Hispanic, one was mixed Hispanic and American Indian, three were Asian or mixed Asian and Caucasian, and one was African-American. Eight of the 10 patients were men. All patients were in the chronic, recurrent phase of their disease when they had subretinal fibrosis develop, and all patients had recurrent episodes of posterior uveitis. Presenting vision ranged from 20/20 to light perception, with a median acuity of 20/200. All patients were initially treated with oral and topical corticosteroids. Four patients required additional noncorticosteroid immunosuppressive therapy. Time from diagnosis of VKH disease to development of subretinal fibrosis ranged from zero (fibrosis present at time of diagnosis) to 27 years, with a median time of 10 months. The median time from diagnosis of VKH to development of subretinal fibrosis in Hispanic patients was 6.5 months, whereas in non-Hispanic patients it was 6.5 years. Final vision ranged from 20/25 to light perception, with a median acuity of 20/60. Seven of 20 eyes had a final visual acuity of 20/40 or better, and seven eyes saw 20/200 or worse. Five of the eyes with 20/200 or worse vision had fibrosis involving the fovea. Conclusions Subretinal fibrosis occurs in a sizeable proportion of patients with VKH disease and may contribute to permanent loss of vision.

Objective To describe three patients who developed Vogt-Koyanagi-Harada syndrome (VKH) after cutaneous injury. Design Retrospective case series. Participants Three patients seen in the uveitis clinic at Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, India, participated. Main outcome measures The history, evaluation, and management of the three patients were summarized. Results Three patients developed VKH syndrome shortly after cutaneous injury. In each case, the affected area of skin became vitiliginous on healing and simultaneous with the onset of ocular symptoms. One patient developed additional ectopic areas of vitiligo. All three patients developed chronic, bilateral, diffuse uveitis, one associated with an exudative retinal detachment and two with Dalen-Fuchs-like nodules. Well-recognized complications of VKH syndrome that occurred in the authors' patients included geographic atrophy of the retinal pigment epithelium (3 of 3), cataract (3 of 3), and glaucoma (1 of 3). Ocular inflammation was well controlled in each patient with local or systemic corticosteroids or both. In one patient, the area of vitiligo showed increased pigmentation in response to systemic corticosteroid treatment. Conclusions Vogt-Koyanagi-Harada syndrome may follow cutaneous injury, supporting the notion that this disorder may result from systemic sensitization to shared melanocytic antigens.

Objective To explore the association between treatment for neovascular age-related macular degeneration (AMD) and incidence and timing of retinal pigment epithelium (RPE) tears in ranibizumab-treated patients versus control treatment. Design Results from 3 phase III clinical trials ( AN ti-VEGF antibody for the treatment of predominantly classic CHOR oidal neovascularization in age-related macular degeneration [ANCHOR], M inimally classic/occult trial of the A nti-VEGF antibody R anibizumab I n the treatment of N eovascular A ge-related macular degeneration [MARINA], and A P hase IIIb, Multicenter, Randomized, Double-Masked, Sham I njection-Controlled Study of the E fficacy and Safety of R anibizumab in Subjects with Subfoveal Choroidal Neovascularization [CNV] with or without Classic CNV Secondary to Age-Related Macular Degeneration [PIER]) were retrospectively reviewed to identify patients who developed RPE tears during the study period, detected on fluorescein angiography performed at prespecified intervals. Participants Patients with baseline and post-baseline angiographic assessments. Methods Patients received intravitreal ranibizumab (0.3 or 0.5 mg) or control treatment (verteporfin photodynamic therapy [PDT] in ANCHOR and sham intravitreal injections in ANCHOR, MARINA, and PIER). Main Outcome Measures Incidence and timing of RPE tears during the treatment period. Results Data from 1298 patients were analyzed. No statistically significant differences in RPE tear incidence were observed. The pooled rate of RPE tears was 1.8% with 0.5 mg ranibizumab, 3.0% with 0.3 mg ranibizumab, and 1.6% in the control group. Most (76%; 16/21) RPE tears in ranibizumab-treated patients were identified within 3 months of initiating treatment, whereas the majority (80%; 4/5) of late-onset RPE tears occurred in control patients. In patients who developed RPE tears, better visual acuity (VA) outcomes were observed in those treated with ranibizumab versus control treatment. Conclusions As studied in these trials, no statistically significant differences in the incidence of RPE tears within a 2-year treatment period were observed in patients who received ranibizumab (0.5 or 0.3 mg) versus control treatment, although most RPE tears with ranibizumab occurred within 3 months of initiating treatment. Mean VA was better in patients who developed RPE tears while receiving ranibizumab than in those who received control treatment, suggesting a potential benefit of continued ranibizumab therapy in patients with neovascular AMD who developed RPE tears. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Objective To describe a patient with oculoleptomeningeal amyloidosis associated with infiltration of the vitreous, elevated intraocular pressures (IOPs), and seizures caused by a TTR Val30Gly mutation in the transthyretin gene. Design Interventional clinicopathologic report. Participant A 44-year-old man with refractory bilateral intermediate uveitis, elevated IOPs, and seizures. Intervention The patient underwent diagnostic pars plana vitrectomy in both eyes. Intraocular and intracerebral pressures were controlled by trabeculectomy and cerebroventricular shunt placement, respectively. Main Outcome Measures Visual acuity, histopathologic analysis of vitreous and leptomeningeal tissue, genetic testing, and magnetic resonance imaging of the brain. Results After failure of the patient to respond to topical and periocular corticosteroid therapy, a pars plana vitrectomy was performed and revealed amorphous material that showed green birefringence and dichroism on Congo red staining, establishing the diagnosis of vitreous amyloidosis. A full medical workup, including genetic testing, revealed a TTR Val30Gly mutation in the transthyretin gene. The patient subsequently developed elevated IOPs requiring bilateral trabeculectomy surgery and episodic seizures associated with leptomeningeal enhancement on magnetic resonance imaging. Histopathological analysis of a leptomeningeal biopsy taken at the time of surgery revealed amyloid infiltration, confirming the diagnosis of oculoleptomeningeal involvement by his amyloidosis. A ventriculoperitoneal shunt was placed. Conclusion Amyloidosis should be considered in patients who present with vitritis that is unresponsive to corticosteroid therapy. Vitreous biopsy with histopathological analysis is recommended in these cases. Additionally, sequencing of the transthyretin gene should be considered in patients with vitreous amyloidosis to help establish known genetic syndromes and predict both ocular and systemic comorbidities. Although not described previously, elevated IOP may develop in patients with vitreous amyloidosis due to a TTR Val30Gly mutation in the transthyretin gene.

Objective To evaluate the safety and efficacy of pegaptanib sodium injection (pegaptanib) in the treatment of diabetic macular edema (DME). Design Randomized, double-masked, multicenter, dose-ranging, controlled trial. Participants Individuals with a best-corrected visual acuity (VA) between 20/50 and 20/320 in the study eye and DME involving the center of the macula for whom the investigator judged photocoagulation could be safely withheld for 16 weeks. Intervention Intravitreous pegaptanib (0.3 mg, 1 mg, 3 mg) or sham injections at study entry, week 6, and week 12 with additional injections and/or focal photocoagulation as needed for another 18 weeks. Final assessments were conducted at week 36. Main outcome measures Best-corrected VA, central retinal thickness at the center point of the central subfield as assessed by optical coherence tomography measurement, and additional therapy with photocoagulation between weeks 12 and 36. Results One hundred seventy-two patients appeared balanced for baseline demographic and ocular characteristics. Median VA was better at week 36 with 0.3 mg (20/50), as compared with sham (20/63) (P = 0.04). A larger proportion of those receiving 0.3 mg gained VAs of > or =10 letters (approximately 2 lines) (34% vs. 10%, P = 0.003) and > or =15 letters (18% vs. 7%, P = 0.12). Mean central retinal thickness decreased by 68 microm with 0.3 mg, versus an increase of 4 microm with sham (P = 0.02). Larger proportions of those receiving 0.3 mg had an absolute decrease of both > or =100 microm (42% vs. 16%, P = 0.02) and > or =75 microm (49% vs. 19%, P = 0.008). Photocoagulation was deemed necessary in fewer subjects in each pegaptanib arm (0.3 mg vs. sham, 25% vs. 48%; P = 0.04). All pegaptanib doses were well tolerated. Endophthalmitis occurred in 1 of 652 injections (0.15%/injection; i.e., 1/130 [0.8%] pegaptanib subjects) and was not associated with severe visual loss. Conclusions In this phase II trial, subjects assigned to pegaptanib had better VA outcomes, were more likely to show reduction in central retinal thickness, and were deemed less likely to need additional therapy with photocoagulation at follow-up.

Purpose To describe the demographic and clinical characteristics of central serous chorioretinopathy (CSC) after solid organ transplantation. Design Case series. Participants Fifteen patients who presented to the authors with CSC after solid organ transplantation. Methods We performed a retrospective chart review to identify patient demographics and clinical features of disease, including angiographic changes. Main Outcome Measures Patterns of CSC. These patterns were compared with type of organ received, demographics, and visual outcome. Results We identified 25 eyes of 7 women (46.7%) and 8 men (53.3%) that developed CSC after solid organ transplantation. Patient ages ranged from 27 to 55 years (median, 40). Seven of the 15 patients (46.7%) were Caucasian, including 3 Hispanic patients (20%). Of the 8 remaining patients (53.3%), 2 were African American (13.3%), 2 were Filipino (13.3%), and 4 were Asian (26.7%). The organs received included 13 kidneys (86.7%), 1 liver (6.7%), and 1 heart (6.7%). Systemic hypertension was reported in 14 of 15 patients (93.3%). All patients were receiving systemic immunosuppressive drugs at presentation; 14 of 15 (93.3%) were also receiving systemic corticosteroids. Visual acuity at presentation ranged from 20/20 to counting fingers. Patterns of CSC included (1) geographic or diffuse alterations in the retinal pigment epithelium (5 eyes; 2 bilateral, 1 unilateral), (2) focal CSC (6 eyes, all unilateral), (3) multifocal CSC (6 eyes; 2 bilateral, 2 unilateral), and (4) CSC with bullous retinal detachment (8 eyes, all bilateral). Follow-up, available for 21 affected eyes of 13 patients, ranged from 1 month to 6 years (median, 12 months). Compared with other solid organ transplant recipients at our institutions, renal transplant recipients ( P = 0.003), as well as Hispanic and Asian patients ( P = 0.05), were more prevalent in this cohort. Conclusion Central serous chorioretinopathy after solid organ transplantation varies in presentation and severity. Our observations support a role for choroidal vascular compromise in the pathogenesis of this disorder.

Objective This study aimed to describe the clinical and histopathologic findings in four patients with complex limbal choristomas associated with linear nevus sebaceous syndrome (LNSS), a rare disorder including nevus sebaceous, seizures, and mental retardation, and often accompanied by ocular anomalies. Design Small observational case series. Methods A retrospective review of the clinical and histopathologic records of four patients. Results Each of four patients had complex limbal choristomas in the setting of clinical and histopathologic LNSS. The limbal choristomas were multiple in three patients and bilateral in two patients. Most choristomas involved the superotemporal limbus (6 of 10), although nasal (3 of 10) and inferior (1 of 10) limbal tumors also were present. Three patients had significant corneal astigmatism or involvement of the central cornea requiring surgical removal of their choristomas, one accompanied by a lamellar keratoplasty and another accompanied by two consecutive penetrating keratoplasties. Each graft eventually vascularized, reducing vision. One patient's vision was limited by amblyopia and another by occipital cortical dysgenesis with visual impairment. Histopathologic examination of the excised choristomas showed foci of lacrimal gland (3 of 4 patients), adipose tissue (3 of 4), neural tissue (1 of 4), cartilage (1 of 4), lymphoid follicles (1 of 4), skin adnexal tissue (1 of 4), and smooth muscle (1 of 4). Other associated ocular findings included an eyelid mass (1 of 4), colobomas of the eyelid (3 of 4), colobomas of the choroid and retina (2 of 4), nonparalytic strabismus (2 of 4), scleral ectasia (1 of 4), partial oculomotor palsy with ptosis and anisocoria (1 of 4), microphthalmia (1 of 4), and cortical visual impairment (1 of 4). Conclusions Complex limbal choristomas, although rare, can occur in the setting of LNSS and can be associated with multiple ocular and systemic abnormalities. Visual prognosis appears poor in most cases despite aggressive management.

Purpose: To describe three patients with systemic lupus erythematosus in whom ophthalmoscopic and fluorescein angiographic evidence of central serous chorioretinopathy developed. Methods: The authors retrospectively reviewed the clinical and photographic records of three patients with systemic lupus erythematous in whom central serous chorioretinopathy developed. Results: Ophthalmoscopic changes observed in these patients with systemic lupus erythematosus included discrete areas of clumping and mottling of the retinal pigment epithelium (RPE), focal RPE detachments, serous elevations of the neurosensory retina, and late subretinal fibrosis with scar formation. Fluorescein angiographic findings included transmission hypofluorescence and hyperfluorescence corresponding to focal RPE alterations, early punctate intense hyperfluorescence corresponding to RPE leaks with progressive filling of sub-RPE detachment spaces, and slow late filling of subretinal detachment spaces. Conclusion: Patients with systemic lupus erythematosus are at increased risk to have central serous chorioretinopathy develop. The pathogenetic implications for an association between systemic lupus erythematosus and central serous chorioretinopathy as well as the similarity to the chorioretinopathy seen with accelerated hypertension, pregnancy, hemodialysis, organ transplantation, and exogenous and endogenous hypercortisolism are discussed. Focal choroidal vasculature compromise with secondary dysfunction of overlying RPE cells is the proposed common mechanism.

OBJECTIVE: To evaluate the efficacy of a second year of pegaptanib sodium therapy in patients with neovascular age-related macular degeneration (AMD). DESIGN: Two concurrent, multicenter, randomized, double-masked, sham-controlled studies (V.I.S.I.O.N. [Vascular Endothelial Growth Factor Inhibition Study in Ocular Neovascularization] trials). PARTICIPANTS: Patients with all angiographic neovascular lesion compositions of AMD were enrolled. In combined analyses, 88% (1053/1190) were re-randomized at week 54, and 89% (941/1053) were assessed at week 102. INTERVENTIONS: At week 54, those initially assigned to pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks (8 injections). Those initially assigned to sham were re-randomized to continue sham, discontinue sham, or receive 1 of 3 pegaptanib doses. MAIN OUTCOME MEASURES: Mean change in visual acuity (VA) over time and mean change in the standardized area under the curve of VA and proportions of patients experiencing a loss of > or =15 letters from week 54 to week 102; losing or =0, > or =1, > or =2, and > or =3 lines of VA; and progressing to legal blindness (20/200 or worse). RESULTS: In combined analysis, mean VA was maintained in patients continuing with 0.3-mg pegaptanib compared with those discontinuing therapy or receiving usual care. In patients who continued pegaptanib, the proportion who lost >15 letters from baseline in the period from week 54 to week 102 was half (7%) that of patients who discontinued pegaptanib or remained on usual care (14% for each). Kaplan-Meier analysis showed that patients continuing 0.3-mg pegaptanib for a second year were less likely to lose > or =15 letters than those re-randomized to discontinue after 1 year (P