Long-term Visual Outcomes and Causes of Vision Loss in Chronic Central Serous Chorioretinopathy.

PURPOSE: To evaluate the long-term visual outcomes and causes of vision loss in chronic central serous chorioretinopathy (CSC). DESIGN: Retrospective, longitudinal study. PARTICIPANTS: A total of 133 participants (217 eyes) with chronic CSC. METHODS: A retrospective review of clinical and multimodal imaging data of patients with chronic CSC managed by 3 of the authors between May 1977 and March 2018. Multimodal imaging comprised color photography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence (FAF), and OCT. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at the final visit; change in BCVA between first visit and 1-, 5-, and 10-year follow-up visits; and causes of vision loss at final visit. RESULTS: Data from 6228 individual clinic visits were analyzed. Mean age of patients at the first visit was 60.7 years, and mean period of follow-up from first to last visit was 11.3 years. The cohort included 101 male patients (75.9%). At the final visit, 106 patients (79.7%) maintained driving-standard vision with BCVA of 20/40 or better in at least 1 eye, and 17 patients (12.8%) were legally blind with BCVA of 20/200 or worse in both eyes. Mean BCVA at first visit was not significantly different from mean BCVA at 1- or 5-year follow-up visits (both P ≥ 0.65) but was significantly better than the mean BCVA at the 10-year follow-up visit (P = 0.04). Seventy-nine percent of eyes with 20/40 or better vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Ninety-two percent of eyes with 20/200 or worse vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Cystoid macular degeneration, choroidal neovascularization (CNV), outer retinal disruption on OCT, and FAF changes were associated with poorer vision at the final visit (all P ≤ 0.001). Multivariable analysis revealed that greater age at first visit was associated with greater BCVA change at the 10-year follow-up visit (P = 0.001). CONCLUSIONS: Chronic CSC can be a sight-threatening disease leading to legal blindness. Age at presentation and outer retinal changes on multimodal imaging were associated with long-term BCVA changes and may be predictors of long-term visual outcomes.

Initial Real-World Experience with Faricimab in Treatment-Resistant Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate the initial efficacy and safety of intravitreal faricimab in eyes previously treated for neovascular age-related macular degeneration (nARMD). Patients and methods: A retrospective review of all patients with nARMD previously treated with anti-vascular endothelial growth factor (anti-VEGF) injections who received at least 3 intravitreal faricimab injections with at least 3 months of follow-up. Results: A total of 190 eyes were included. Patients received a mean of 34.2±23 anti-VEGF injections over 182.41±128 weeks prior to switching to faricimab. Patients then received a mean of 6.99±2.3 faricimab injections with an average 34.88±8.2 weeks of follow-up. The mean best corrected visual acuities improved from 0.33±0.32 logMAR ≈20/43 to 0.27±0.32 logMAR ≈20/37 (P=0.0022). The central subfield thickness (CST) improved from 312±87µm to 287±71µm (P<0.0001). At the last clinical visit, 24% had no subretinal fluid or intraretinal fluid on optical coherence tomography. The mean dosing interval between the last two consecutive faricimab injections (7.64±6.2 weeks) was significantly longer than that for ranibizumab (5.16±2.0 weeks, P<0.001) or aflibercept (5.57±3.6 weeks, P<0.001). No patients developed idiopathic intraocular inflammation. Conclusion: Intravitreal faricimab was associated with improved vision and CSTs, even in treatment-resistant nARMD eyes. The mean last dosing interval for faricimab was longer than for ranibizumab or aflibercept. No significant adverse events were directly attributed to faricimab during the study.

Heterotopic Purkinje cells in ataxia-telangiectasia.

Ataxia-telangiectasia (A-T) is a heritable disorder of cerebellar ataxia and oculocutaneous telangiectasias caused by mutation of the ATM gene. The most prominent and consistent neuropathologic finding in the disorder is cerebellar cortical degeneration involving significant loss of granule and Purkinje cells. Several past autopsy studies of A-T patients have also noted large-bodied cells located within the molecular layer of the cerebellar cortex and, noting similarities in morphology between these cells and Purkinje cells, hypothesized that the cells were heterotopic Purkinje cells. This study aimed to test this hypothesis using an antibody that labels Purkinje cells, and also to investigate other cell types in the degenerating cerebellar cortex in A-T. Using the anti-calbindin D-28K antibody to label Purkinje cells in cerebellar tissue from five A-T patients and five age- and sex-matched controls, the study found calbindin-positive heterotopic Purkinje cells in the molecular layer occurring at a significantly higher rate in A-T patients than in controls (P = 0.012). Further immunohistochemistry with the anti-Iba-1 and anti-parvalbumin antibodies showed, respectively, an increase in microglial activity (P = 0.14) and stellate-cell density (P = 0.0048) in the cerebellar cortex of A-T patients versus controls. These data add to the as yet unresolved debate over the origin and significance of heterotopic Purkinje cells in A-T.

Purtscher-Like Retinopathy in a Patient with COVID-19.

The emerging literature on the novel coronavirus pandemic has reported several cases of varied retinal findings in patients with COVID-19. We report the case of a 59-year-old male who presented with complaint of bilateral blurry vision following hospital discharge after prolonged hospitalization for severe COVID-19 illness. On ocular exam, the patient demonstrated bilateral cotton wool spots localized to the posterior pole of each eye. Multimodal imaging demonstrated findings consistent with retinal nerve fiber layer infarcts in the areas of the cotton wool spots. Exam and imaging of our patient were most consistent with a Purtscher-like retinopathy. We suggest that as ophthalmologists care for increasing numbers of patients recuperating from COVID-19, they monitor for microangiopathic changes similar to those in our patient.

Long-Term Outcomes in Macular Telangiectasia Type 2 With Subretinal Neovascularization.

Purpose: This work reports long-term outcomes in macular telangiectasia type 2 (MacTel) with subretinal neovascularization (SRNV). Methods: A retrospective, single-center review of medical records was performed on all patients with a diagnosis of MacTel presenting between May 2004 and October 2019. Medical and ocular history, best-corrected visual acuity (BCVA) at baseline and final visit, optical coherence tomography data, and treatment history of SRNV secondary to MacTel were recorded. Results: A total of 471 eyes were diagnosed with MacTel. SRNV was present in 44 eyes (9.3%), of which 38 eyes met inclusion criteria for SRNV. Average follow-up duration in the SRNV group was 78.4 months. All SRNV patients underwent antivascular endothelial growth factor (anti-VEGF) therapy. There was no significant change from mean baseline (0.59 ± 0.45) to final (0.70 ± 0.49) BCVA in the SRNV group as a whole (P = .13). Subgroup analysis revealed 17 of 38 eyes had SRNV at diagnosis and received immediate anti-VEGF treatment. In this subgroup mean pretreatment BCVA was 0.89 ± 0.43 and the mean final BCVA was 0.87 ± 0.61 (P = .84). The remainder (21 of 38 eyes) developed SRNV during follow-up. In this subgroup, final BCVA after initiation of treatment was 0.56 ± 0.32, an improvement in BCVA from SRNV onset (P = .04) and a decrease from pre-SRNV onset baseline BCVA (P = .008). Conclusions: Visual acuity is maintained, not improved, in long-term follow-up of MacTel with SRNV treated with anti-VEGF. Patients presenting with SRNV have a worse prognosis than those who develop SRNV during follow-up.

Increased activation of Iba1+ microglia in pediatric epilepsy patients with Rasmussen's encephalitis compared with cortical dysplasia and tuberous sclerosis complex.

Microgliosis is prominent in Rasmussen's encephalitis (RE), a disease with severe seizure activity. However, it is unclear if microglial activation is similar with different histopathologic substrates. Iba1-immunolabelled microglial activation was assessed in neocortex from pediatric epilepsy surgery patients with RE (n=8), cortical dysplasia (CD; n=6) and tuberous sclerosis complex (TSC; n=6). Microglial reactivity was increased, in severely affected RE areas (29% labeling) compared with minimally affected areas of RE cases (15%) and cases of TSC (14%) and CD (12%). There was no qualitative association of Iba1 immunolabelling with the presence of CD8(+) cytotoxic T-cells and no statistical association with clinical epilepsy variables, such as seizure duration or frequency. Iba1 appears to be an excellent marker for detecting extensive microglial activation in patients with RE. In addition, this study supports the notion that Iba1-labeled microglial activation is increased in patients with active RE, compared with cases of CD and TSC.

Long-Term Multimodal Imaging of Solar Retinopathy.

This is a rare, multimodal imaging report spanning a decade of monitoring in a patient with chronic solar retinopathy showing the natural course of the disease. Spectral-domain optical coherence tomography (SD-OCT) showed mild widening of subfoveal loss of ellipsoid and interdigitation zones bilaterally, progressive retinal pigment epithelial thinning in the right eye, and hyperplasia in the left eye. Structural en face OCT showed subfoveal tissue loss bilaterally. There was no leakage on fluorescein angiography and OCT angiography (OCTA), and dense B-scan OCTA images were unremarkable. Microperimetry revealed bilateral decreased central sensitivity and eccentric fixation in the left eye. Vision remained stable throughout. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:388-392.].

Reverse Argentinean flag sign: Intraoperative complication during capsulorhexis.

We report a case of iatrogenic creation of an excessive anterior-to-posterior gradient in the setting of an open anterior capsule during capsulorhexis. This complication shows the inverse mechanism of that observed in the Argentinean flag sign. An excessive anterior-to-posterior gradient from an exuberant ophthalmic viscosurgical device fill of the anterior chamber caused radialization of the anterior capsule during creation of a continuous curvilinear capsulorhexis in a nonintumescent lens. We describe this complication as the reverse Argentinean flag sign.

Unilateral Ocular Manifestations of Vogt-Koyanagi-Harada Disease.

PURPOSE: To describe a case of unilateral Vogt-Koyanagi-Harada (VKH) disease and associated multimodal imaging. METHODS: Retrospective case report. RESULTS: A 50-year-old Hispanic male presented with three days of painless decreased vision in his left eye, headache, and decreased hearing. His visual acuity was 20/20 in the right eye and counting fingers in the left eye. Examination of his right eye was unremarkable. Funduscopic examination of his left eye revealed multiple serous retinal detachments. Fluorescein angiography demonstrated late multifocal pinpoint hyperfluorescence in his left eye and a diagnosis of VKH disease was made. He was treated with oral prednisone. Serial re-examination demonstrated resolution of the serous retinal detachments and a taper of his oral prednisone was initiated with improvement of his visual acuity to 20/25. CONCLUSIONS: Our patient had imaging and a clinical course that was consistent with VKH disease. This unilateral presentation may represent a clinical variant of VKH disease.

The Age-Related Macular Degeneration Complex: Linking Epidemiology and Histopathology Using the Minnesota Grading System (The Inaugural Frederick C. Blodi Lecture).

PURPOSE: To describe the histopathologic findings of the four stages of age-related macular degeneration (AMD) as defined by the Age-Related Eye Disease Study (AREDS) using the Minnesota grading system (MGS). CLINICAL RELEVANCE: There are no animal models for AMD. Eye banks enable access to human tissue with AMD. The level of AMD (grades 1 through 4) as defined by AREDS is determined ex vivo using the MGS. The AREDS has the largest collection to date of prospectively gathered data on the natural history of AMD. Since the MGS uses the same clinical criteria as AREDS, the addition of histopathologic findings of graded tissue confirms important pathophysiology at each stage of AMD. METHODS: Four eye bank eyes were graded according to the MGS. Only the right eyes were dissected for phenotype grading. The fellow (left) eyes were fixed for histopathologic study. The eyes were serially sectioned (7 µm) through the macula. Individual slides were examined, and a two-dimensional reconstruction of the topography of the macula was created for each donor. Selected, unstained slides were used for immunohistochemical staining. In one donor, portions of tissue were obtained for transmission electron microscopic (TEM) processing. RESULTS: Donor 1 had a rare hard, nodular druse (MGS1). Donor 2 had intermediate confluent drusen (MGS2). Donor 3 had numerous intermediate drusen (MGS3) in the right eye. Histopathology of the fellow left showed basal laminar deposits (BLamD), soft drusen, and an area of occult choroidal neovascularization underlying the retinal pigment epithelium (RPE) with endothelial cells (CD31-positive). Donor 4 also had MGS 3 along with reticular pseudodrusen (RPD). Histologic and TEM examination demonstrated diffuse BLamD, thickening of Bruch's membrane, hard drusen, and focal nodules underlying the RPE that corresponded to the RPD. EM examination demonstrated both BLamD and electron-dense material located just external to the elastic layer of Bruch's membrane. CONCLUSION: Eye bank eyes graded using the MGS serve as an important link to the phenotypic and epidemiologic data from the AREDS. Thus, the MGS serves as a system to study the histopathology at each stage of AMD to better understand the relevant pathophysiologic changes in disease progression.