CORRELATION BETWEEN MICROPERIMETRY AND IMAGING IN EXTENSIVE MACULAR ATROPHY WITH PSEUDODRUSEN-LIKE APPEARANCE.

PURPOSE: To determine the correlation between microperimetry and imaging findings in extensive macular atrophy with pseudodrusen-like appearance (EMAP). METHODS: This cross-sectional, observational study included 44 consecutive patients with EMAP (88 eyes) and 30 healthy subjects (60 eyes). Both groups underwent visual acuity assessment, mesopic and scotopic microperimetry, fundus photography, autofluorescence, optical coherence tomography, and optical coherence tomography angiography. Retinal sensitivity was also subdivided in macular (0-4°) and paramacular areas (8-10°). Scotopic sensitivity loss was defined as the difference between scotopic and mesopic sensitivities for each tested point. Eyes with EMAP were further classified into the three stages described by Romano et al: 19 eyes in Stage 1, 31 in Stage 2, and 38 in Stage 3. RESULTS: Mesopic and scotopic retinal sensitivity were significantly reduced in patients with EMAP compared with controls, particularly in the macular area (all P < 0.001). Mesopic retinal sensitivity progressively declined in more advanced EMAP stages (all P < 0.01), but no scotopic differences were observed between Stages 2 and 3 ( P = 0.08). Remarkably, scotopic sensitivity loss was significantly higher in Stage 1 ( P < 0.05).On multivariate analysis, mesopic dysfunction was associated with larger atrophic areas ( P < 0.01), foveal involvement ( P = 0.03), and fibrosis ( P = 0.02). Conversely, no independent variable was associated with a reduced scotopic retinal sensitivity (all P > 0.05). CONCLUSION: The findings highlight that patients with EMAP suffer from a severe cone- and rod-mediated dysfunction on microperimetry. The predominant rod impairment in the early cases (Stage 1) emphasizes the importance of dark-adapted scotopic microperimetry as a clinical end point and suggests defective transportation across the RPE-Bruch membrane complex in its pathogenesis.

Diabetic retinopathy in the pediatric population: Pathophysiology, screening, current and future treatments.

Diabetic retinopathy (DR) is a sight threatening complication of diabetes mellitus (DM). The incidence of DR in the pediatric population has increased in the last two decades and it is expected to further rise in the future, following the increase in DM prevalence and obesity in youth. As early stages of the retinal disease are asymptomatic, screening programs are of extreme importance to guarantee a prompt diagnosis and avoid progression to more advanced, sight threatening stages. The management of DR comprises a wide range of actions starting from glycemic control, continuing with systemic and local medical treatments, up to para-surgical and surgical approaches to deal with the more aggressive complications. In this review we will describe the pathophysiology of DR trying to understand all the possible targets for currently available or future treatments. We will briefly consider the impact of screening techniques, screening strategies and their social and economic impact. Finally a large part of the review will be dedicated to medical and surgical treatments for DR including both currently available and under development therapies. Most of the available data in the literature on DR are focused on the adult population. The aim of our work is to provide clinicians and researchers with a comprehensive overview of the state of the art regarding DR in the pediatric population, considering the increasing numbers of this diseases in youth and the inevitable consequences that such a chronic disease could have if poorly managed in children.

CORRELATION BETWEEN INFLAMMATORY FOCI REACTIVATION AND ATROPHY GROWTH IN EYES WITH IDIOPATHIC MULTIFOCAL CHOROIDITIS.

PURPOSE: To correlate the number of inflammatory reactivations in atrophic foci of multifocal choroiditis (MFC) with their growth rate over a 4-year span. METHODS: Comparative case series. Optical coherence tomography scans of patients affected by MFC were reviewed to identify reactivations within or at the margin of atrophic MFC foci. The area of selected lesions was semiautomatically delineated on fundus autofluorescence images and recorded at yearly intervals for a total follow-up of 4 years. The main outcome was the difference in annual square-root transformed area growth rate between lesions that reactivated and lesions that did not. RESULTS: Sixty-six foci of 30 eyes of 24 patients were included. All MFC foci enlarged over time, but the annual growth rate was more than double in lesions that reactivated compared with those that did not (mean [SD], 0.051 [0.035] vs. 0.021 [0.015] mm/year, P < 0.001), despite starting from comparable baseline areas. For each additional inflammatory reactivation, the annual growth rate increased by more than 20% (+0.009 mm/year, 95% CI [0.006, 0.012], P < 0.001). CONCLUSION: Increasing number of reactivations of atrophic foci led to proportional increments in their growth rate, highlighting the need for a tight control of inflammatory relapses in patients affected by MFC.

Automated quantification of uveitic keratic precipitates by use of anterior segment optical coherence tomography.

BACKGROUND: Evaluation of ocular inflammation via common imaging modalities like optical coherence tomography (OCT) has emphasised cell visualisation, but automated detection of uveitic keratic precipitates (KPs) remains unexplored. METHODS: Anterior segment (AS)-OCT dense volumes of the corneas of patients with uveitic KPs were collected at three timepoints: with active (T0), clinically improving (T1), and resolved (T2) inflammation. At each visit, visual acuity and clinical grading of the anterior chamber cells were assessed. A bespoke algorithm was used to create an en face rendering of the KPs and to calculate their volume and a ratio of the volume of precipitates over the analysed area. The variation of AS-OCT-derived measurements over time was assessed, and compared with clinical grading. RESULTS: Twenty eyes from 20 patients (13 females, mean age 39 years) were studied. At T0, the mean volume of the corneal KPs was 0.1727 mm3 , and it significantly reduced to 0.1111 mm3 (p = 0.03) only at T2. The ratio between the volume of the KPs and the corneal area decreased from T0 (0.007) to T1 (0.006; p = 0.2) and T2 (0.004; p = 0.009). There was a statistically significant correlation between the AC cell count and the AS-OCT volume measurements of the KPs at the three time points. CONCLUSIONS: AS-OCT can image uveitic KPs and through a bespoke algorithm we were able to create an en face rendering allowing us to extrapolate their volume. We found that objective quantification of KPs correlated with inflammatory cell counts in the anterior chamber.

Twenty-four-month real-life treatment outcomes of polypoidal choroidal vasculopathy versus type 1 macular neovascularization in Caucasians.

BACKGROUND: To compare 24-month real-world outcomes of Vascular Endothelial Growth Factor (VEGF) inhibitors for Polypoidal Choroidal Vasculopathy (PCV) and type 1 Macular Neovascularization (MNV) in a Caucasian population. METHODS: Retrospective analysis from a prospectively designed observational database. Data from Italian centres participating in the Fight Retinal Blindness! (FRB!) project were collected. Treatment-naïve PCV or type 1 MNV commencing treatment after January 2009 were included. The primary outcome was 24-month visual acuity (VA) change; other outcomes included baseline characteristics, number of anti-VEGF injections, time to lesion inactivation and proportion of active visits. RESULTS: A total of 322 eyes (114 PCVs) from 291 patients were included. Median [Q1, Q3] VA at baseline was comparable (70 [55, 75.8] vs. 70 [58.8, 75] letters, p = 0.95). Adjusted VA change at 2 years was higher in PCV (mean [95% CI], +1.2 [-1.6, 4.1] vs. -3.6 [-6, -1.2] letters, p = 0.005). PCV received fewer anti-VEGF injections over the first 24 months of treatment than type 1 MNV (median [Q1, Q3], 8 [5, 10] vs. 9 [7, 12.2] injections, p = 0.001), inactivated earlier (median [Q1, Q3], 235 [184, 308] vs. 252 [169, 343] days, p = 0.04) and was less frequently graded 'active' (62% vs. 68% of visits, p = 0.001). CONCLUSIONS: PCV had slightly better VA outcomes over 24 months of treatment than type 1 MNV after receiving less anti-VEGF injections. These results suggest a possible overlap of the two clinical entities with similar visual prognosis in Caucasians.

Prechoroidal cleft thickness correlates with disease activity in neovascular age-related macular degeneration.

PURPOSE: The purpose of this study was to investigate the structural variations of the hyporeflective pocket of fluid (prechoroidal cleft) located between Bruch's membrane and the hyperreflective material within the pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (nAMD). METHODS: In this retrospective, observational case series study, patients diagnosed with nAMD and prechoroidal cleft associated with other activity signs of the macular neovascularization (MNV) were included. Structural optical coherence tomography (OCT) scans were evaluated to obtain anatomical measurements of prechoroidal cleft and PED at three different visits (T0, inactive MNV; T1, active MNV; T2, treated inactive MNV). The variations in size of the cleft and the PED were correlated with nAMD activity. RESULTS: Twenty-nine eyes from 27 patients were included. The subfoveal measurements showed a significant increase of prechoroidal cleft height and width from T0 to T1 (P < 0.05) and a subsequent decrease of the cleft height after treatment with anti-VEGF agents (P = 0.004). A similar significant trend was observed for the greatest prechoroidal cleft height and width, obtained assessing the whole OCT raster. In the multivariate analysis, the cleft height was significantly affected by both time (P = 0.001) and PED height (P < 0.0001). By contrast, the effect of fibrovascular tissue size within the PED was not significant. Visual acuity did not correlate with prechoroidal cleft size. CONCLUSION: Prechoroidal cleft increased in association with MNV reactivation and decreased after treatment. Our results suggest that prechoroidal cleft could represent an accumulation of fluid actively exudating from the MNV and should be considered a sign of nAMD activity.

LONGITUDINAL FOLLOW-UP OF CHOROIDAL GRANULOMAS WITH INDOCYANINE GREEN ANGIOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: A Lesion-Based Analysis.

PURPOSE: To investigate choroidal granulomas visualized by indocyanine green angiography (ICGA) and optical coherence tomography angiography (OCTA) in response to treatment. METHODS: Ten eyes of eight patients with tubercular, sarcoid, or Vogt-Koyanagi-Harada-associated choroidal granulomas were evaluated in this multicentric study. All patients underwent ICGA and OCTA at baseline, 1, and 3 months after treatment onset. Granulomas were identified as hypofluorescent lesions on intermediate ICGA phases. Late ICGA behavior and OCTA visualization were assessed. RESULTS: On baseline intermediate ICGA, 222 choroidal granulomas were detected. Overall, 174/222 granulomas were detected on baseline OCTA images. At 1 month, 28% of lesions were healed and 48 late ICGA hyperfluorescent lesions were identified. At 3 months, 63% of baseline lesions were healed, with 33 persistent late hyperfluorescent lesions. Optical coherence tomography angiography sensitivity was reduced at 1 and 3 months compared with baseline. Some flow-voids detected on OCTA at 1 and 3 months did not correspond to any visible lesion on ICGA. CONCLUSION: Different healing behaviors of choroidal granulomas were identified combining ICGA and OCTA analysis. Late ICGA hyper-fluorescent lesions may be the consequence of a possible fibrotic shift. Structural changes in the choroid may persist after active granulomas resolution resulting in persistent flow voids on OCTA.

MULTIMODAL IMAGING CHARACTERISTICS AND FUNCTIONAL CORRELATES IN RIP HEALING.

PURPOSE: To report the imaging and functional features of the repair tissue following retinal pigment epithelium (RPE) tears. METHODS: This cross-sectional observational study included patients with RPE tears secondary to neovascular age-related macular degeneration and at least 12 months of follow-up. The following variables were analyzed: best-corrected visual acuity; retinal sensitivity using microperimetry; outer retinal layers status and RPE resurfacing on optical coherence tomography; fibrosis; autofluorescence signal recovery using blue-light and near-infrared autofluorescence. RESULTS: Overall, 48 eyes were included (age: 82 ± 5 years) and 34 of them showed signs of healing. Retinal pigment epithelium resurfacing was noticed in 22 cases, whereas fibrosis appeared in 21 eyes. Autofluorescence improved in 17 cases using blue-light infrared autofluorescence and 7 eyes on near-infrared autofluorescence. Outer retinal layers were more frequently preserved when RPE resurfacing and autofluorescence improvement occurred ( P < 0.05). Although best-corrected visual acuity was higher for smaller RPE tears ( P = 0.01), retinal sensitivity of the healing tissue was positively affected by autofluorescence improvement ( P < 0.001) and by absence of fibrosis ( P = 0.03). CONCLUSION: Autofluorescence signal recovery after rip occurrence possibly reflects the underlying status of the RPE and is associated with better functional outcomes. Our findings highlight the importance of blue-light infrared autofluorescence and especially near-infrared autofluorescence assessment in the setting of rip healing.

INTERNATIONAL IMPACT OF THE COVID-19 PANDEMIC LOCKDOWN ON INTRAVITREAL THERAPY OUTCOMES: Fight Retinal Blindness Registry.

PURPOSE: To evaluate the impact of the COVID-19 pandemic lockdowns on the outcomes of eyes treated for neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion in eight countries. METHODS: A multicenter international database study of 5,782 eyes (4,708 patients) receiving intravitreal antivascular endothelial growth factor injections before, during, and after national lockdowns. The baseline visit was defined as the last visit within 3 months before lockdown, and prelockdown and postlockdown periods were defined as 6 months before and after the lockdown date. RESULTS: Eyes with neovascular age-related macular degeneration (n = 4,649) lost vision in all countries in proportion to the reduced number of injections. The mean visual acuity change postlockdown ranged from -0.4 to -3.8 logarithm of the minimum angle of resolution letters, and the median number of injections/visits decreased from 4-5/4-7 to 2-4/2-4 postlockdown. The diabetic macular edema (n = 654) and retinal vein occlusion (n = 479) eyes' mean visual acuity change ranged from -2.8 to +1.7 letters and -1.6 to +0.1 letters, and the median number of injections/visits decreased from 2.5-5/4-6 to 1-3/2-4 and from 3-5.5/4-5 to 1-3.5/2-3.5, respectively. The 6-month dropout rates postlockdown were 20% for neovascular age-related macular degeneration, 27% for diabetic macular edema, and 28% for retinal vein occlusion. CONCLUSION: This international study provides estimates of the impact of COVID-19 pandemic lockdown on intravitreal therapy and suggests that prioritizing neovascular age-related macular degeneration eyes seems appropriate.

Quantitative autofluorescence findings in patients undergoing hydroxychloroquine treatment.

BACKGROUND: To measure quantitative autofluorescence (qAF) in patients under treatment with hydroxychloroquine (HCQ) and at risk of retinal toxicity but with no apparent signs of retinal toxicity and to compare it with that of untreated subjects. METHODS: Consecutive patients at risk for the development of HCQ retinal toxicity (duration of treatment >5 years or daily HCQ dose >5 mg/kg of actual body weight [ABW]) but no alterations on spectral domain-optical coherence tomography, short-wavelength autofluorescence and 10-2 visual field examination were recruited. Healthy subjects matched by age and sex were also enrolled in the study. All subjects underwent qAF measurements in one eye. Images were analysed using the conventional qAF grid by Delori calculating the qAF of eight sectors of the intermediate ring and the mean of those values (qAF8 ). RESULTS: Thirty-nine patients treated with HCQ (38 females, mean age 52.1 ± 8.6 years) and 39 untreated subjects (38 females, mean age 51.2 ± 8.6 years) were included. In both HCQ patients and untreated subjects, qAF8 was positively correlated with age (p = 0.004). Although HCQ patients showed a higher mean qAF8 compared with untreated subjects (294.7 ± 65.3 vs. 268.9 ± 57.5), the difference was not significant (p = 0.068). HCQ patients showed significantly higher mean qAF values in the inferior-temporal, inferior and inferior-nasal sectors of the intermediate ring of qAF grid compared with untreated subjects (all p < 0.05). CONCLUSIONS: These results suggest a possible preclinical increase of qAF values in inferior parafoveal sectors probably induced by HCQ exposure.

Polypoidal Choroidal Vasculopathy: Consensus Nomenclature and Non-Indocyanine Green Angiograph Diagnostic Criteria from the Asia-Pacific Ocular Imaging Society PCV Workgroup.

PURPOSE: To develop consensus terminology in the setting of polypoidal choroidal vasculopathy (PCV) and to develop and validate a set of diagnostic criteria not requiring indocyanine green angiography (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photography findings. DESIGN: Evaluation of diagnostic test results. PARTICIPANTS: Panel of retina specialists. METHODS: As part of the Asia-Pacific Ocular Imaging Society, an international group of experts surveyed and discussed the published literature regarding the current nomenclature and lesion components for PCV, and proposed an updated consensus nomenclature that reflects our latest understanding based on imaging and histologic reports. The workgroup evaluated a set of diagnostic features based on OCT images and color fundus photographs for PCV that may distinguish it from typical nAMD and assessed the performance of individual and combinations of these non-ICGA features, aiming to propose a new set of diagnostic criteria that does not require the use of ICGA. The final recommendation was validated in 80 eyes from 2 additional cohorts. MAIN OUTCOME MEASURES: Consensus nomenclature system for PCV lesion components and non-ICGA-based criteria to differentiate PCV from typical nAMD. RESULTS: The workgroup recommended the terms polypoidal lesion and branching neovascular network for the 2 key lesion components in PCV. For the diagnosis of PCV, the combination of 3 OCT-based major criteria (sub-retinal pigment epithelium [RPE] ring-like lesion, en face OCT complex RPE elevation, and sharp-peaked PED) achieved an area under the receiver operating characteristic curve of 0.90. Validation of this new scheme in a separate subset 80 eyes achieved an accuracy of 82%. CONCLUSIONS: We propose updated terminology for PCV lesion components that better reflects the nature of these lesions and is based on international consensus. A set of practical diagnostic criteria applied easily to spectral-domain OCT results can be used for diagnosing PCV with high accuracy in clinical settings in which ICGA is not performed routinely.

Optical coherence tomography angiography for detection of macular neovascularization associated with atrophy in age-related macular degeneration.

PURPOSE: To evaluate the ability of optical coherence tomography angiography (OCTA) to detect macular neovascularization (MNV) in eyes with atrophy compared with fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). METHODS: In this prospective study, eyes with MNV and atrophy (termed macular atrophy or MA) secondary to age-related macular degeneration (AMD), and AMD eyes with geographic atrophy (GA) without MNV underwent multimodal imaging with FA, ICGA, structural OCT, and OCTA. The presence of MNV was determined using all imaging modalities by senior retina specialists and was considered the gold standard reference. Each individual imaging modality was then evaluated independently by two expert readers for the presence of MNV in a masked fashion. Morphologic characteristics of the MNV were evaluated on the custom OCTA slab. RESULTS: Twenty-one patients with MA+MNV and 21 with GA only were enrolled. Manual segmentation on OCTA allowed detection of the MNV in 95.2% of eyes with MA+MNV and in 4.7% of eyes with GA, showing high specificity (95.2%) and sensitivity (95.2%). FA, ICGA, and OCT detected MNV in 57.1%, 52.3%, and 66.7% of eyes with MA+MNV and in 14.2%, 9.5%, and 42.8% with GA. Sensitivity and specificity were 85.7% and 57.1% for FA, 90.5% and 52.4% for ICGA, and 66.7% and 57.1% for OCT. CONCLUSIONS: OCTA appears to be superior to other imaging modalities for identification of MNV in eyes with macular atrophy. OCTA should be considered as part of the multimodal imaging evaluation of eyes with atrophy, particularly in the context of clinical trials.

Sutureless scleral fixation: comparison between 3-piece IOL and new single-piece foldable IOL.

PURPOSE: Comparing two different sutureless scleral fixation techniques. METHODS: A retrospective study of patients who underwent sutureless scleral fixation IOL from October 2013 to May 2018 at "Luigi Sacco Hospital", University of Milan. Comparison between two groups: Group 1 implanted with a 3-piece ALCON-MA60AC and group 2 implanted with a newly developed single-piece foldable IOL SOLEKO FIL-SSF. Patients underwent a complete preoperative ophthalmic assessment and post-operative evaluation at 1, 3, and 6 months. Vitrectomy was performed in all cases. The two groups were compared for age, axial length, and lens status at baseline. Visual acuity, refractive results, surgical time, and post-operative complications were recorded. RESULTS: Thirty-one eyes were included: group 1, 15 eyes of 15 patients, and group 2, 16 eyes of 14 patients. No difference was found in visual acuity. Mean refractive error was 1D in both groups (group 1 1.01D, group 2 1.09D), but spherical equivalent was more often moved toward negative values and induced astigmatism was greater in the 3-piece group (group 1 1.91D [SD ± 2.07], group 2 0.67D [SD ± 0.88] P = 0.04). Surgical procedure was faster in group 2 (mean time difference 21', P = 0.01*). New displacement occurred in 5 cases (33%) of group 1 and in no cases of group 2 (P = 0.01*). Post-operative bleeding was registered only in group 1 (20%), but the difference was not statistically significant. CONCLUSIONS: The group 2 IOL gives in our sample better results due to less post-operative astigmatism and reducing dislocation and bleeding during follow-up. Surgical technique appeared easier and faster: the specifically designed IOL seems to be a feasible solution for sutureless scleral fixation.

IMPACT OF CORONAVIRUS DISEASE PANDEMIC ON INTRAVITREAL INJECTIONS TREATMENT FOR MACULAR DISEASES: Report From a Referral Hospital in Milan.

PURPOSE: To describe our managing strategy for COVID-19 emergency, to evaluate the adherence to intravitreal treatment (AtT) rate during the outbreak in a referral hospital in Milan, and to correlate it with patients' clinical features. METHODS: The AtT rate of patients with scheduled intravitreal injections during the COVID-19 outbreak from February 23, 2020 to March 31, 2020 was compared with the previous trimester and with March 2019. The impact of age, sex, visual function, and diagnosis on the AtT rate during unlocked/locked weeks (from March 8th) was evaluated. RESULTS: Of 650 consecutive patients with scheduled intravitreal injections, the AtT rate during the COVID-19 outbreak was 0.37. This was significantly lower compared with AtT registered in the previous trimester (0.92) and in the same weeks in 2019 (0.90) (both P < 0.001). Patients adherent to treatment were significantly younger (P < 0.001) and had a lower best-corrected visual acuity in the fellow eye (P = 0.046). During the lockdown weeks, the AtT rate was significantly lower than in the two unlocked weeks (0.19 vs. 0.73, P < 0.001). In addition, the AtT rate in patients classified as "emergent" during the lockdown weeks was 0.60. CONCLUSION: These preliminary results can help the retina specialist community to foresee this unique scenario and to develop successful management strategies.

CHOROIDAL GRANULOMAS VISUALIZED BY SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To assess the visualization of choroidal granulomas with swept-source optical coherence tomography angiography (OCTA). METHODS: Consecutive patients with granulomatous choroiditis due to tuberculosis, sarcoidosis, or Vogt-Koyanagi-Harada disease underwent baseline OCTA images using a 12 × 12-mm field of view, and the choroidal slabs were analyzed by two independent examiners who counted the oval areas of flow void. Simultaneously, indocyanine green angiography (ICGA) and enhanced-depth imaging OCT were performed to mark visible choroidal changes corresponding to granulomatous lesions. The lesion areas on OCTA and ICGA were assessed using the in-built caliper tool. RESULTS: Three hundred and one round-shaped areas of flow void on OCTA, 209 hypofluorescent round lesions on ICGA, and 42 hyporeflective choroidal lesions on enhanced-depth imaging OCT were identified in 23 eyes from 14 patients. Of the 209 ICGA granulomas, 197 (94.3%) had a corresponding round area of flow void on OCTA that was interpreted as a granuloma. One hundred and four additional round flow voids were identified on OCTA that did not correspond to any hypofluorescent lesion on ICGA. The mean area of the 197 granulomas detected with both imaging modalities was significantly larger on ICGA (mean 0.33 mm2) than that on OCTA (mean 0.28 mm2). CONCLUSION: Optical coherence tomography angiography seems to be an optimal imaging method for the visualization of choroidal granulomas.

LONGITUDINAL FOLLOW-UP OF TUBERCULAR SERPIGINOUS-LIKE CHOROIDITIS USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To analyze and describe serial follow-up of choriocapillaris alterations in tubercular serpiginouslike choroiditis (SLC) using optical coherence tomography angiography (OCTA) and to compare it with multimodal imaging. METHODS: In this prospective cohort study, patients with active tubercular SLC underwent OCTA using Optovue RTVue XR Avanti and other imaging techniques including enhanced-depth imaging OCT (EDI-OCT) (Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany), fundus autofluorescence, fluorescein angiography, and indocyanine green angiography. Serial imaging was performed for a total follow-up of 3 months. Choriocapillaris alterations at the site of lesions were analyzed on OCTA imaging, and their mean lesion areas were calculated. RESULTS: Twenty-six eyes (26 patients; 20 males; mean age: 32.68 ± 10.56 years) were included. Fourteen eyes had active multifocal lesions (n = 39), whereas 12 eyes had active placoid lesions (n = 12). At baseline, OCTA showed hyporeflective flow deficit lesions corresponding to the hypofluorescent lesions on indocyanine green angiography in all eyes. In the multifocal type of SLC, the mean lesion area decreased in all eyes compared with baseline, and lesions with a lesion area less than 0.1 mm2 on OCTA showed near-complete resolution with minimal choriocapillaris atrophy. In comparison, all eyes with a placoid type of SLC showed no significant reduction in the lesion area and showed extensive choriocapillaris atrophy. CONCLUSION: Optical coherence tomography angiography has the unique ability to demonstrate pathological flow impairment at the level of choriocapillaris in active tubercular SLC. Serial OCTA analysis reveals that large tubercular SLC lesions result in choriocapillaris atrophy as the lesions heal, whereas smaller multifocal lesions show resolution of choriocapillaris hypoperfusion with minimal atrophy.

OPTICAL COHERENCE TOMOGRAPHY FEATURES OF CHOROIDAL NEOVASCULARIZATION AND THEIR CORRELATION WITH AGE, GENDER, AND UNDERLYING DISEASE.

PURPOSE: To investigate the influence of age, gender, and underlying disease on the optical coherence tomography (OCT) features of choroidal neovascularization (CNV) secondary to inflammation, myopia (mCNV), and age-related macular degeneration (AMD-CNV). METHODS: Demographic and clinical data of eyes with treatment-naive inflammatory CNV, mCNV, and Type 2 AMD-CNV were collected. Optical coherence tomography images were reviewed to determine the presence of pitchfork sign, pigment epithelial detachment, subretinal fluid (SRF), intraretinal cysts, subretinal hyperreflective material, atrophy, and outer retinal disruption graded 1 to 4. The influence of demographics and underlying etiology on OCT signs was investigated. RESULTS: One hundred and eighty-five eyes from 179 patients were enrolled. The mean [SD] age was 36 [±14.4], 62 [±18], and 77 [±8] for the inflammatory CNV, mCNV, and AMD-CNV, respectively (P < 0.001). Multiple linear regression showed that the presence of pitchfork sign was negatively associated with age (P < 0.0001), regardless of underlying disease. By contrast, the SRF, pigment epithelial detachment, intraretinal cysts, and the outer retinal disruption were all positively influenced by age, regardless of gender and underlying disease (all P < 0.01). Logistic regression showed that none of the OCT signs increased the likelihood for diagnosis of inflammatory CNV. By contrast, the absence of SRF was suggestive for mCNVs, and the presence of pigment epithelial detachment and SRF was suggestive for AMD-CNVs. CONCLUSION: The age of the patient had a significant effect on the OCT appearance of the CNV, particularly the presence of a pitchfork sign, regardless of the underlying etiology. The absence of SRF was suggestive for a diagnosis of mCNVs. The presence of SRF and pigment epithelial detachment was suggestive for AMD-CNVs.

Macular Atrophy Incidence and Progression in Eyes with Neovascular Age-Related Macular Degeneration Treated with Vascular Endothelial Growth Factor Inhibitors Using a Treat-and-Extend or a Pro Re Nata Regimen: Four-Year Results of the MANEX Study.

PURPOSE: To compare the incidence and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a treat-and-extend (T&E) or a pro re nata (PRN) regimen over 4 years in a real-world setting. DESIGN: Four-year, multicenter, retrospective comparative study. PARTICIPANTS: Two hundred sixty-four patients with treatment-naive nAMD. METHODS: Consecutive patients with nAMD received anti-VEGF therapy according to a T&E (n = 163) or PRN (n = 101) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had undergone annual fundus autofluorescence (FAF) and OCT imaging using Heidelberg Spectralis. Two masked graders independently delineated areas of MA from serial FAF images using Heidelberg region finder software, and growth rates were calculated. Incident MA was assessed using proportional hazard ratios. MAIN OUTCOMES MEASURES: Macular atrophy incidence and progression over 4 years, association between treatment strategies, and number of injections. RESULTS: At baseline, MA was present in 24% and 20% of study eyes in T&E and PRN groups, respectively (P = 0.45). At year 4, 27% (34/124) and 25% (20/81) of eyes without baseline MA showed detectable MA in the T&E and PRN groups, respectively. In those with MA at baseline, the mean square root area of MA progressed by a rate of 0.4 ± 0.2 mm/year and 0.4 ± 0.1 mm/year in the T&E and PRN groups, respectively (P = 0.23). Multivariate analysis for baseline predictors of MA growth demonstrated that older age, poorer baseline visual acuity, and presence of retinal angiomatous proliferation had a higher risk of greater MA progression (P = 0.03). Regression analysis demonstrated no association between T&E and PRN treatment strategies with the risk of new MA developing during the 4 years of follow-up or the progression of pre-existing MA at year 4 (P = 0.692). CONCLUSIONS: Over 4 years, neither incidence nor progression of MA in eyes with nAMD treated with anti-VEGF injections was influenced by the treatment regimen and injection frequency. Eyes treated with a T&E regimen received more injections and achieved better visual outcomes compared with those treated with a PRN approach.

Demyelination precedes axonal loss in the transneuronal spread of human neurodegenerative disease.

The spread of neurodegeneration through the human brain network is reported as underlying the progression of neurodegenerative disorders. However, the exact mechanisms remain unknown. The human visual pathway is characterized by its unique hierarchical architecture and, therefore, represents an ideal model to study trans-synaptic degeneration, in contrast to the complexity in neural connectivity of the whole brain. Here we show in two specifically selected patient cohorts, including (i) glaucoma patients with symmetrical bilateral hemifield defects respecting the horizontal meridian (n = 25, 14 females, 64.8 ± 10.1 years; versus 13 normal controls with similar age/sex distributions); and (ii) multiple sclerosis patients without optic radiation lesions (to avoid potential effects of lesions on diffusivity measures) (n = 30, 25 females, 37.9 ± 10.8 years; versus 20 controls), that there are measurable topographic changes in the posterior visual pathways corresponding to the primary optic nerve defects. A significant anisotropic increase of water diffusion was detected in both patient cohorts in the optic radiations, characterized by changes in perpendicular (radial) diffusivity (a measure of myelin integrity) that extended more posteriorly than those observed in parallel (axial) diffusivity (reflecting axonal integrity). In glaucoma, which is not considered a demyelinating disease, the observed increase in radial diffusivity within the optic radiations was validated by topographically linked delay of visual evoked potential latency, a functional measure of demyelination. Radial diffusivity change in the optic radiations was also associated with an asymmetrical reduction in the thickness of the calcarine cortex in glaucoma. In addition, 3 years longitudinal observation of the multiple sclerosis patient cohort revealed an anterograde increase of radial diffusivity in the anterior part of optic radiations which again was retinotopically associated with the primary damage caused by optic neuritis. Finally, in an animal model of optic nerve injury, we observed early glial activation and demyelination in the posterior visual projections, evidenced by the presence of myelin-laden macrophages. This occurred prior to the appearance of amyloid precursor protein accumulation, an indicator of disrupted fast axonal transport. This study demonstrated strong topographical spread of neurodegeneration along recognized neural projections and showed that myelin and glial pathology precedes axonal loss in the process, suggesting that the mechanism of trans-synaptic damage may be at least partially mediated by glial components at the cellular level. The findings may have broad biological and therapeutic implications for other neurodegenerative disorders.

Biomarkers in Usher syndrome: ultra-widefield fundus autofluorescence and optical coherence tomography findings and their correlation with visual acuity and electrophysiology findings.

PURPOSE: To investigate the functional and structural biomarkers and their correlation with Usher syndrome (USH). METHODS: Medical records, imaging and electrophysiology test results of USH patients attending the Save Sight Institute between 2012 and 2017 were reviewed. Best corrected visual acuity (BCVA), ultra-widefield autofluorescence (UW-FAF), spectral-domain optical coherence tomography (SD-OCT), full-field electroretinogram and pattern electroretinogram (pERG) were performed. SD-OCT scans assessed central macular thickness (CMT), greatest linear diameter of preserved outer retinal layers-macular island (MI) and presence of cystoid macular edema (CME). UW-FAF images were qualitatively graded to identify hypo/hyperfluorescence patterns in the peripheral fundus. RESULTS: Thirty-six eyes from 18 subjects were included. Mean BCVA was 0.22 ± 0.3 LogMAR. MI extent was significantly associated with better vision (ß = - 0.175 per 1000 µm; R2 = 0.487; P = 0.002; Fig. 4). A higher pERG P50 was associated with a larger macular island (ß = 782 per µV; R2 = 0.238; P = 0.025), while a higher pERG N95 was associated with a smaller macular island (ß = - 499 per µV; R2 = 0.219; P = 0.030). Mean CMT was 271 ± 35 µm and was significantly associated with better vision (ß = - 0.083 per 10 µm; R2 = 0.612; P < 0.001). CME was diagnosed in 47.2% (n = 17) eyes. There was no significant difference in mean BCVA for those with CME (0.19 ± 0.2 LogMAR) and without CME (0.40 ± 0.5; R2 = 0.081; P = 0.17). All patients had abnormal UW-FAF. Four main patterns of change were identified (granular 55%, annular 11%, bone spicule 17% and patchy 17%). Patients with the patchy pattern demonstrated worse BCVA in comparison with those with granular (P < 0.0001) and bone spicule (P = 0.0179) patterns. CONCLUSIONS: Structural changes identified on OCT and UW-FAF correlated with BCVA and pERG in this cohort representing different stages of the disease. These parameters could represent reliable biomarkers in therapeutic clinical trials on USH.