Ophthalmic vascular manifestations in eosinophil-associated diseases: a comprehensive analysis of 57 patients from the CEREO and EESG networks and a literature review.

Introduction: Eosinophils have widespread procoagulant effects. In daily practice, eosinophil-related cardiovascular toxicity consists of endomyocardial damage, eosinophilic vasculitis and arterial or venous thrombosis. Here we aim to report on the clinical features and treatment outcomes of patients with unexplained ophthalmic vascular manifestations and eosinophilia. Methods: We conducted a retrospective, multicenter, observational study and a literature review of patients with eosinophilia (≥0.5 x109/L) and concomitant ophthalmic vascular manifestations independent of the underlying eosinophilic disease but with no alternative cause for ophthalmic manifestations. Results: Fifty-seven patients were included (20 from the observational study and 37 from the literature review). Ophthalmic vascular features were the initial manifestation of eosinophil-related disease in 34 (59%) patients and consisted of 29 central retinal artery occlusions, six branch retinal artery occlusions, five central retinal vein occlusions, two branch retinal vein occlusions, seven retinal vasculitides, two retinal vasospasms, 12 Purtscher's retinopathies, 13 anterior ischemic optic neuropathies and two posterior ischemic optic neuropathies. The median [IQR] absolute eosinophil count at onset of ophthalmic vascular manifestations was 3.5 [1.7-7.8] x109/L. Underlying eosinophil-related diseases included eosinophilic granulomatosis with polyangiitis (n=32), clonal hypereosinophilic syndrome (HES) (n=1), idiopathic HES (n=13), lymphocytic HES (n=2), adverse drug reactions (n=3), parasitosis (n=2), polyarteritis nodosa (n=1), IgG4-related disease (n=1), eosinophilic fasciitis (n=1) and primary sclerosing cholangitis (n=1). Other extra-ophthalmologic arterial or venous thromboses related to eosinophilia were reported in four (7%) and nine (16%) patients, respectively. Visual prognosis was poor: only eight (10%) patients achieved full recovery of ophthalmologic symptoms. After a median follow-up of 10.5 [1-18] months, one patient (3%) had a recurrence of an ophthalmic vascular manifestation, and three patients (10%) had a recurrence of other vascular symptoms (deep vein thrombosis in two and pulmonary embolism in one patient). At the time of recurrence, absolute eosinophil counts were above 0.5 x109/L in all cases (n=4). Discussion: This study broadens the spectrum of vascular manifestations associated with hypereosinophilia by adding ophthalmic vascular manifestations. In patients with ophthalmological vascular manifestations and hypereosinophilia, aggressive treatment of the underlying pathology (and normalization of blood count) should be implemented.

Retinal Ischemic Perivascular Lesions Are Associated With Myocardial Infarction in Patients With Coronary Artery Disease.

PURPOSE: To evaluate the association of retinal ischemic perivascular lesions (RIPLs) with myocardial infarction (MI) among patients diagnosed with coronary artery diseases (CAD). DESIGN: Retrospective cross-sectional study. METHODS: Consecutive patients (317 patients) with CAD who underwent macular spectral domain optical coherence tomography (SD-OCT) were captured. Patients with CAD who developed MI were compared to those without MI. SD-OCT were reviewed by 2 independent and masked graders for the presence of RIPLs. Medical records were reviewed. Multivariate logistic regression analysis was used to evaluate the relationship between RIPLs and MI including the following covariates age, gender, smoking status, hypertension, diabetes, dyslipidemia and body mass index. RESULTS: Of 317 patients with CAD for whom OCT scans were available to study, there were 54 (17%) with a history of MI. A higher prevalence of RIPLs was observed in the MI group compared to the non-MI group (59.3% vs 35.7%; P < .001). The presence of RIPLs was significantly associated with MI with an odds ratio of 3 (1.91-4.74; P < .001), after adjusting for age, gender, smoking status, hypertension, diabetes, dyslipidemia, and body mass index. CONCLUSIONS: The presence of RIPLs, detected with SD-OCT, is significantly associated with MI in patients with CAD. These findings underscore the potential clinical utility of incorporating RIPL evaluation in the medical management of CAD.

Cystoid macular edema as a complication of central retinal artery occlusion.

Purpose: To describe the development of cystoid macular edema (CME) as a complication of central retinal artery occlusion (CRAO) in 2 cases. Observations: The first patient was a 51-year-old female who presented with acute loss of vision in the left eye. Multimodal retinal imaging revealed a CRAO with a perfused cilioretinal artery. CME acutely developed one week after presentation. Cystoid spaces predominantly involved the outer nuclear layer (ONL) on optical coherence tomography (OCT) and completely resolved in two weeks. The second case was a 50-year-old man who presented with acute vision loss in the right eye for 3 weeks. Multimodal retinal imaging illustrated an acute CRAO of the right eye. Four weeks later, visual acuity spontaneously improved to 20/20 and was maintained at 20/20 for more than 2 years. After 28 months, the patient returned with a recurrent drop of vision in the right eye. Cross sectional and en face OCT revealed CME in the right eye without leakage on FA. Cystoid spaces predominantly involved the inner nuclear layer (INL) and resolved with intravitreal anti-VEGF injection combined with carbonic anhydrase inhibitor (CAI) and steroid topical drop therapy. Conclusions and Importance: CME can rarely complicate both the acute and chronic phase of CRAO. In the acute phase, cystoid spaces were transient and confined to the ONL on OCT. While in the chronic phase, cystoid spaces were confined to the INL on OCT and angiographically silent on FA. Further studies are needed to identify the incidence, underlying pathophysiology and visual prognosis of CME in cases of CRAO.

En Face Optical Coherence Tomography Illustrates the Trizonal Distribution of Drusen and Subretinal Drusenoid Deposits in the Macula.

PURPOSE: To analyze the topographic distribution of macular drusen and subretinal drusenoid deposits (SDDs) using single-capture en face spectral domain optical coherence tomography (SD-OCT) imaging. DESIGN: Retrospective case series. METHODS: Analysis of 33 eyes of 20 patients with evidence of SDDs. Structural en face OCT images were reconstructed using a 40-µm-thick slab positioned from 48 to 88 µm above the Bruch membrane. The Early Treatment of Diabetic Retinopathy Study (ETDRS) grid and a rod/cone density map were overlaid on the en face OCT images, and the distribution of different subtypes of SDDs and macular drusen were assessed. RESULTS: A total of 31 eyes (94%) showed a trizonal distribution pattern of drusen and SDDs. Whereas small to large drusen tended to aggregate in the central circle, dot SDDs predominated in the inner ring and the inner portion of the outer ring of the ETDRS grid and ribbon SDDs localized to the outer ring and outside the ETDRS grid. Of note, drusen colocalized to the region of greatest cone density, whereas ribbon SDDs colocalized to the area of greatest rod density. The dot SDDs mapped to the intermediate region with mixed rod and cone representation. CONCLUSION: Dot and ribbon subtypes of SDDs and macular drusen show a characteristic trizonal distribution. The locations of these lesions colocalize according to the different densities of the cones and rods in the retina and may reflect varying pathophysiological activities of these photoreceptor subtypes.

FROM DRUSEN TO TYPE 3 MACULAR NEOVASCULARIZATION.

PURPOSE: To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography. METHOD: From a cohort of eyes with T3 MNV and ≥ 12 months of previously tracked spectral-domain optical coherence tomography, T3 lesions that developed above soft drusen were selected for optical coherence tomography analysis. Retinal imaging findings at the location where type T3 MNV occurred were analyzed at each follow-up until the onset of T3 MNV. The following optical coherence tomography parameters were assessed: drusen size (height and width), outer nuclear layer/Henle fiber layer thickness at the drusen apex, and the presence of intraretinal hyperreflective foci, retinal pigment epithelium disruption, incomplete retinal pigment epithelium and outer retina atrophy, and complete retinal pigment epithelium and outer retina atrophy. RESULTS: From a cohort of 31 eyes with T3 MNV, T3 lesions developed above soft drusen in 20 eyes (64.5%). Drusen showed progressive growth ( P < 0.001) associated with outer nuclear layer/Henle fiber ( P < 0.001) thinning before T3 MNV. The following optical coherence tomography features were identified preceding the occurrence of T3 MNV, typically at the apex of the drusenoid lesion: disruption of the external limiting membrane/ellipsoid zone and/or the retinal pigment epithelium, hyperreflective foci, and incomplete retinal pigment epithelium and outer retina atrophy/complete retinal pigment epithelium and outer retina atrophy. CONCLUSION: The results demonstrate specific anatomic alterations preceding the occurrence of T3 MNV that most commonly originates above soft drusen. Drusen growth, reduced outer nuclear layer/Henle fiber thickness, and retinal pigment epithelium atrophy at the drusen apex precede the development of T3 MNV. Identifying these optical coherence tomography features should warrant close monitoring for identification of T3 MNV, which can benefit from prompt intravitreal anti-vascular endothelial growth factor therapy.

32-year-old diabetic patient with progressive vision loss and crystalline retinopathy.

PURPOSE: To report the case of severe bilateral retinal vascular occlusion in a patient with hyperoxalosis and chronic renal failure. METHODS: Observational case report. Medical and imaging records were retrospectively reviewed. The patient was imaged with ultra-widefield (UWF) fundus photography and fluorescein angiography (UWF-FA), cross sectional and en face spectral-domain optical coherence tomography (SD-OCT), and OCT angiography. RESULTS: A 32-year-old diabetic patient receiving peritoneal dialysis was referred because of severe vision loss. UWF color fundus photography showed diffuse sclerotic retinal vessels and diffuse intraretinal crystals in both eyes. UWF-FA illustrated near-complete retinal vascular occlusion and capillary wipe out in both eyes. SD-OCT demonstrated diffuse inner and middle retina thinning in both eyes and multiple intraretinal hyperreflective foci consistent with crystalline deposits in all retina layers of both eyes. OCT angiography revealed severe capillary and large vessel non-perfusion in the superficial and deep retinal capillary plexus of each eye. The serum oxalate levels were increased at 28 µmol/L (reference range < 2 µmol/L) and genetic testing was positive for a heterozygous mutation of the AGXT (Alanine-Glyoxylate Amino Transferase) gene that causes type 1 autosomal recessive primary hyperoxaluria. CONCLUSION: A diagnosis of hyperoxalosis causing severe retinal vascular occlusion was rendered. Hyperoxalosis was the result of multiple factors including heterozygous AGXT mutation, chronic renal failure insufficiently treated with peritoneal dialysis, and a diet high in oxalate. This case highlights the importance of ruling out retinal oxalosis in patients on peritoneal dialysis in order to initiate prompt hemodialysis and prevent severe retinal vascular occlusion.

Ocular steroidome in human eyes and in eyes with complex central serous chorioretinopathy (CSCR).

The exact link between systemic and ocular endogenous corticoids (steroidome) is unclear and whether the ocular steroidome is altered in CSCR eyes is unknown. The aims of this study were to analyze the human steroidome in the aqueous humor as a function of age, sex and time of the day, to correlate systemic and ocular steroidome and to analyze the ocular steroidome in long lasting complex inactive CSCR. Based on our results, we present two CSCR cases treated by the combination of oral mineralocorticoid antagonist and glucocorticoids drops. In a cross-sectional study, aqueous humor (AH) was collected between 8am and 6 pm from 50 unaffected individuals (25 men and 25 women) and from 14 patients with chronic CSCR, during cataract surgery. In addition, simultaneous serum and AH were collected from 27 individuals undergoing cataract surgery and, simultaneous AH and vitreous were collected from 9 patients undergoing cataract and vitrectomy to estimate corticoids levels in the different compartments. The steroidome was determined using a LC-MS/MS method that quantifies 13 endogenous corticoids from the gluco, mineralocorticoid and androgen pathways. In AH and vitreous, the highest corticoid level is reached by cortisol (F), that represents less than 10% of F serum level. The cortisol levels in the serum did not correlate with ocular cortisol levels. Serum and ocular cortisone (E) levels correlate, although less than 5% of circulating E reaches the eye. The only mineralocorticoids measured in the AH were corticosterone (B) and its inactive form, the 11-desoxycorticosterone (A). There was no influence of circadian rhythm on cortisol ocular levels and there was no correlation between the age or the sex and the level of F, E, A, and B. In eyes with chronic inactive CSCR, the levels of the active glucocorticoid form F was lower than in control eyes and the F/E ratio was reduced by 50% but the B/A ratio was higher indicating imbalance towards active mineralocorticoids. Base on this observation, we propose to combine an antagonist of the mineralocorticoid receptor together with topical glucocorticoids in two CSCR patients, resistant to all other treatments, with favorable outcome. Our results indicate that the ocular psteroidome is highly regulated suggesting a local metabolism of ocular corticoids. In eyes with long-lasting complex inactive CSCR, the steroidome analysis shows lower active glucocorticoids and higher active mineralocorticoids.

EVALUATION OF PARAVASCULAR INNER RETINAL DEFECTS USING EN FACE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To evaluate the prevalence and risk factors for development of paravascular inner retinal defects (PIRDs) using en face optical coherence tomography. METHODS: This is a retrospective cross-sectional study. En face and cross-sectional optical coherence tomography images were reviewed (9 × 9 mm or 12 × 12 mm). Paravascular inner retinal defects were classified as either Grade 1 (i.e., paravascular inner retinal cysts) when the lesion was confined within the nerve fiber layer without any communication to the vitreous cavity or Grade 2 (i.e., paravascular lamellar hole) when the defects communicated to the vitreous. Paravascular inner retinal defect grading was correlated with presence of high myopia, stage of posterior vitreous detachment, and presence of epiretinal membrane and retinoschisis. RESULTS: Of 1,074 patients (2,148 eyes), PIRDs were detected in 261 eyes with a prevalence of 261 per 2,148 eyes (12.2%) and 176 per 1,074 patients (16.4%). A total of 116 eyes (44.4%) displayed Grade 2 PIRDs while 145 eyes (55.6%) were Grade 1. In the multivariate logistic regression model, the presence of partial/complete posterior vitreous detachment, retinoschisis, and epiretinal membrane was significantly correlated with PIRDs (OR = 2.78 [1.7-4.4], P < 0.001; OR = 2.93 [1.7-5], P < 0.001; and OR = 25.9 [2.8-242.5], P < 0.001, respectively). The presence of partial/complete posterior vitreous detachment and epiretinal membrane was also significantly associated with Grade 2 PIRDs versus Grade 1 PIRDs ( P = 0.03 and P < 0.001). CONCLUSION: Our results indicate that wide-field en face optical coherence tomography facilitates the identification of PIRDs over a large area of retina with a single capture. The presence of PIRDs was significantly associated with posterior vitreous detachment, epiretinal membrane, and retinoschisis, confirming the role of vitreoretinal traction in the pathogenesis of PIRDs.

Progression of Pentosan Polysulfate Sodium Maculopathy in a Prospective Cohort.

PURPOSE: To describe the progression of pentosan polysulfate sodium (PPS) maculopathy after drug discontinuation qualitatively and quantitatively using multimodal imaging assessmen. DESIGN: Prospective case series. METHODS: Patients with PPS maculopathy were evaluated after discontinuation of PPS. Near-infrared reflectance (NIR), fundus autofluorescence (FAF), and optical coherence tomography (OCT) were evaluated in all patients at baseline and at the final follow-up visit at least 12 months later. A qualitative and quantitative analysis of the retinal imaging findings was performed. Patterns of disease progression were evaluated. Area of disease involvement on FAF, retinal pigment epithelium (RPE) atrophy on FAF and NIR, and retinal layer thicknesses on OCT were measured at baseline and at the follow-up visit. RESULTS: A total of 26 eyes were included, with a follow-up period ranging from 13 to 30 months. The diseased area measured on FAF showed significant expansion in all eyes from baseline to follow-up despite drug cessation (P = .03) with a median linearized rate of change of 0.42 mm/y. There was significant reduction in the central macular thickness (P = .04), inner nuclear layer thickness (P = .003), outer nuclear layer thickness (P = .02), and subfoveal choroidal thickness (P = .003) at follow-up vs baseline. New areas of RPE atrophy on FAF in the macula developed in 4 eyes while preexisting atrophic lesions increased in size in 5 eyes. CONCLUSION: Eyes with baseline PPS maculopathy all exhibited remarkable progression with qualitative and quantitative multimodal imaging analysis despite drug discontinuation. Disease progression may be attributed to underlying inner choroidal ischemia or RPE impairment.

Recurrent Anterior Uveitis Associated with Major Fluctuations in Choroidal Thickness in Patient with Pachychoroid Disorder.

PURPOSE: To describe remarkable choroidal thickness fluctuations corresponding to episodes of recurrent anterior uveitis with subretinal fluid development when exceeding a choroidal thickness threshold. METHODS: A patient with pachychoroid pigment epitheliopathy and unilateral acute anterior uveitis of the left eye was evaluated over a period of 3 years with multimodal retinal imaging including optical coherence tomography (OCT). Longitudinal changes in subfoveal choroidal thickness (CT) were measured and correlated with episodes of recurrent inflammation. RESULTS: Over the course of 5 recurrent episodes of inflammation in the left eye treated with oral antiviral and topical steroid therapy, subfoveal CT increased as much as 200 um or more. Subfoveal CT in the fellow quiescent right eye by contrast, was within normal limits and minimally changed throughout the follow up. Increased CT occurred with each episode of anterior uveitis and decreased by 200 µm or more during periods of quiescence in the affected left eye. Subretinal fluid and macular edema developed with a maximum CT of 468 um and spontaneously resolved when CT decreased after treatment. CONCLUSION: In eyes with pachychoroid disease, anterior segment inflammation may lead to marked increases in subfoveal CT and the development of subretinal fluid at a threshold thickness value.

Birdshot Chorioretinitis in Patients Aged 80 and Older.

PURPOSE: To assess the manifestations of birdshot chorioretinitis (BSCR) in patients aged 80 and over. DESIGN: Among patients with BSCR followed in the CO-BIRD prospective cohort (ClinicalTrials.gov Identifier: NCT05153057), we analyzed the subgroup of patients aged 80 and over. METHODS: Patients were assessed in a standardized manner. Confluent atrophy was defined as hypoautofluorescent spots on fundus autofluorescence (FAF). RESULTS: We included 39 (8.8%) of the 442 enrolled CO-BIRD patients. The mean age was 83.8 ± 3.7 years. The mean logMAR BCVA was 0.52 ± 0.76, with 30 patients (76.9%) having 20/40 or better in at least one eye. Thirty-five (89.7%) patients were receiving no treatment. Confluent atrophy in the posterior pole, disrupted retrofoveal ellipsoid zone and choroidal neovascularization were associated with logMAR BCVA >0.3 (p < .0001). CONCLUSION: In patients aged 80 and over we observed a striking heterogeneity of outcomes, but most retained a BCVA that allowed them to drive.

INDOCYANINE GREEN ANGIOGRAPHY OF TYPE 1 MACULAR NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION AND CENTRAL SEROUS CHORIORETINOPATHY REVEALS DIFFERENT DISEASE MECHANISMS.

PURPOSE: To assess the rate of late phase hyperfluorescent plaque (LPHP) in Type 1 macular neovascularization (MNV) in central serous chorioretinopathy (CSCR) and age-related macular degeneration (AMD) and to evaluate its prognostic value. METHODS: Retrospective study including Type 1 MNV in AMD and CSCR, from 2012 to 2020. Eyes with a late indocyanine green angiography image (>20 minutes) and clear visualization of MNV on optical coherence tomography angiography (OCTA) were included. Quantitative and qualitative parameters on optical coherence tomography and best-corrected visual acuity were recorded at baseline and after three monthly antivascular endothelial growth factor injections. RESULTS: Eighty-three eyes were included, 35 with CSCR and 48 with AMD. Patients in the CSCR group were significantly younger than in the AMD group (61.3 ± 10.4 vs. 80.2 ± 6.8 years, respectively, P < 0.001), predominantly male (68.6% CSCR vs. 35.4% AMD; P = 0.003), and with a thicker choroid (379 ± 93.3 µ m vs. 204.2 ± 93.2 µ m; P < 0.001). Type 1 MNV in CSCR showed fewer LPHP compared with AMD (31.4% vs. 77.1%; P < 0.001). The baseline visual acuity was lower in patients with LPHP (0.37 ± 0.22 vs. 0.27 ± 0.28 logarithm of the minimum angle of resolution, P = 0.03). On multivariate analysis, AMD was associated with the presence of LPHP ( P < 0.001). No significant difference in the response to antivascular endothelial growth factor was observed. CONCLUSION: Leakage of macromolecules from MNV and accumulation in the retinal pigment epithelium and/or in the stroma imaged by the LPHP is less common in eyes with Type 1 MNV in CSCR than in AMD. Late phase indocyanine green angiography imaging offers an insight into the metabolism of the dye and the environment surrounding the neovascular membrane.

Corticosteroids Decrease the Incidence and Activity of Choroidal Neovascularization in Patients with Punctuate Inner Choroidopathy or Multifocal Choroiditis.

PURPOSE: To assess the effect of corticosteroids (CS) on choroidal neovascularization (CNV) occurrence and recurrence of activity over 2 years in patients with punctate inner choroidopathy (PIC) or multifocal choroiditis (MFC). METHODS: Retrospective longitudinal study. Previous use of CS was analyzed between group without CNV and group with CNV occurrence and recurrence. RESULTS: Thirty-six patients were included. Patients with CNV were less likely to have received CS in the 6 months following PIC or MFC diagnosis (17% versus 65%, p-value = 0.01). Patients with CNV who had a recurrence of neovascular activity were less likely to have received a previous CS therapy (20% versus 78%; odds ratio = 0.08, p-value = 0.005). CONCLUSIONS: This study suggests that patients with PIC and MFC should be treated by CS to prevent CNV development and decrease CNV recurrences.

High Levels of C-Reactive Protein with Low Levels of Pentraxin 3 as Biomarkers for Central Serous Chorioretinopathy.

Purpose: To investigate the association between the 2 acute phase proteins, C-reactive protein (CRP) and pentraxin 3 (PTX3) with central serous chorioretinopathy (CSCR), as PTX3 is a glucocorticoid-induced protein. Design: Cross-sectional multicenter study. Participants: Patients with CSCR compared with age- and sex-matched healthy participants. Methods: Patients with CSCR from 3 centers in Europe were included in the study. The clinical form of CSCR was recorded. Blood samples from patients with CSCR and healthy participants were sampled, and high-sensitivity CRP and PTX3 levels were measured in the serum. Main Outcome Measures: C-reactive protein and PTX3 serum level comparison between patients with CSCR with age- and sex-matched healthy participants. Results: Although CRP levels were higher in patients with CSCR (n = 216) than in age- and sex-matched controls (n = 130) (2.2 ± 3.2 mg/l vs. 1.5 mg/l ± 1.4, respectively, P = 0.037), PTX3 levels were lower in patients with CSCR (10.5 ± 19.9 pg/ml vs. 87.4 ± 73.2 pg/ml, respectively, P < 0.001). There was no significant difference in CRP or PTX3 levels between patients with acute/recurrent and chronic CSCR. Conclusions: In patients with CSCR, high CRP and low PTX3 levels suggest a form of low-grade systemic inflammation together with a lack of glucocorticoid pathway activation, raising new hypotheses on the pathophysiology of CSCR. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Successful Treatment of Severe Peripapillary Pachychoroid Syndrome with Anti VEGF Therapy.

PURPOSE: To describe two cases of severe peripapillary pachychoroid syndrome (PPS) successfully managed with monthly intravitreal aflibercept therapy. METHODS: Medical and imaging records were retrospectively reviewed. Patients were imaged with ultra-widefield fluorescein and indocyanine green angiography and fundus autofluorescence. Spectral-domain optical coherence tomography (SD-OCT) was performed to evaluate macular edema and choroidal thickness. OCT angiography excluded macular neovascularization. RESULTS: This report summarizes 2 cases of PPS complicated by very severe bilateral macular edema. In all 4 eyes, the diffuse intraretinal and subretinal fluid remarkably improved or completely resolved after monthly intravitreal aflibercept injections with commensurate improvement of visual acuity. Multimodal imaging documented the significant improvement of fluid and the reduction in choroidal thickening in response to anti-VEGF therapy in each case. CONCLUSION: Severe cases of PPS associated with vision loss can be successfully treated with intravitreal aflibercept therapy.

Type 3 macular neovascularization in a patient with pentosan polysulfate maculopathy.

Purpose: To report the development of type 3 macular neovascularization (MNV) in a patient with pentosan polysulfate sodium (PPS) maculopathy one year after PPS cessation. Observation: A 72-year-old woman presented for decreased visual acuity in the left eye. Medical history was significant for interstitial cystitis treated with PPS for 11 years (cumulative dose of 1205 g) and PPS maculopathy. PPS was discontinued 1 year prior to presentation. Blue-light fundus autofluorescence and spectral domain optical coherence tomography confirmed the diagnosis of bilateral PPS maculopathy. OCT-angiography illustrated the development of type 3 MNV with intraretinal fluid in the left eye. Intravitreal injections of aflibercept were initiated with a good visual and anatomical response. Conclusion and importance: This report describes the development of type 3 MNV in a patient with PPS macular toxicity one year after PPS cessation. This complication emphasizes the need for regular retinal surveillance even after discontinuation of the inciting drug.

Non-neovascular fluid in age-related macular degeneration: observe-and-extend regimen in a case-series study.

OBJECTIVE: To describe the course of non-neovascular fluid in age-related macular degeneration (AMD) after anti-vascular endothelial growth factor (anti-VEGF) therapy or after observation without injections. DESIGN: Retrospective case series. METHODS: AMD eyes with macular drusen and (or) drusenoid pigment epithelial detachment associated with non-neovascular fluid were included. Optical coherence tomography (OCT) angiography was performed in all eyes to exclude the presence of macular neovascularization. Subretinal fluid (SRF) was measured to determine the response after anti-VEGF therapy and after observation without injections. RESULTS: Ten eyes of 9 patients with intermediate AMD and SRF were studied over a median period of 59.5 months (range, 7-128 months). Six patients (6 eyes) had a history of anti-VEGF therapy. Median follow-up off injections was 13.5 months (range, 4-44 months). SRF thickness remained stable and unchanged during the follow-up off injections in all eyes (n = 6) with prior injection and in all eyes (n = 4) that had never been injected. Six eyes developed complete retinal pigment epithelial (RPE) and outer retinal atrophy, and 1 eye developed incomplete RPE and outer retinal atrophy. All eyes exhibited at least 2 OCT biomarkers associated with a high risk for progression to atrophy. CONCLUSION: This study provides preliminary data regarding the progression of non-neovascular fluid in AMD with or without anti-VEGF injections. A possible mechanism for fluid development may be related to RPE pump impairment. Distinguishing neovascular versus non-neovascular fluid using multimodal imaging, including OCT angiography, is essential to avoid unnecessary anti-VEGF therapy. An observe-and-extend regimen may be considered in AMD eyes with non-neovascular fluid.

Birdshot Chorioretinopathy: A Review.

Birdshot chorioretinopathy (BSCR) is a bilateral chronic inflammation of the eye with no extraocular manifestations. BSCR affects middle-aged individuals from European descent and is strongly associated with the human leucocyte antigen (HLA)-A29 allele. The immune mechanisms involved are not fully understood, but recent advances have shown the role of Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) in disease pathogenesis. Multimodal imaging, including fluorescein angiography, indocyanine angiography, fundus autofluorescence, and optical coherence tomography, are useful in confirming the diagnosis and monitoring disease activity. Visual field testing is also important to assess the disease progression. To date, there is no consensus for optimal treatment regimen and duration. Local and systemic corticosteroids can be used for short periods, but immunosuppressive or biological therapies are usually needed for the long-term management of the disease. Here, we will review publications focused on birdshot chorioretinopathy to give an update on the pathophysiology, the multimodal imaging, and the treatment of the disease.