RETICULAR PSEUDODRUSEN DISAPPEARANCE AFTER DEVELOPMENT OF MACULAR NEOVASCULARIZATION.

PURPOSE: To explore changes in reticular pseudodrusen (RPD) number and location after the development of macular neovascularization (MNV) in eyes with prior intermediate age-related macular degeneration, focusing on different retinal regions differently affected by MNV. METHODS: This retrospective longitudinal study included intermediate age-related macular degeneration eyes with RPD that developed MNV. Reticular pseudodrusen were assessed at baseline when MNV was diagnosed (MNV stage) and after anti-vascular endothelial growth factor treatment. Three regions of interest were considered: MNV area, subretinal fluid (SRF) area, and a marginal area of 1,000 µm around SRF (marginal zone). Reticular pseudodrusen counts were compared with age- and sex-matched control eyes with RPD that did not develop MNV. RESULTS: Reticular pseudodrusen number exhibited a significant decrease after MNV development in the MNV area (P = 0.048) and in the area with SRF (P = 0.078). A statistically significant decrease was also disclosed in the marginal area around SRF (P = 0.002), associated with larger SRF areas. Control eyes did not show any significant change in the RPD count. CONCLUSION: Reticular pseudodrusen reduction after MNV development suggests a complex interplay involving the MNV itself, the presence of SRF, and trophic changes. The results of this study highlight the role of MNV in retinal nutritional balance and provide intriguing results in the RPD life cycle.

The Silent Masquerade: Clinical and Imaging Features of Asymptomatic Vitreoretinal Lymphoma.

PURPOSE: To report and characterize ocular features of asymptomatic vitreoretinal lymphoma (VRL) associated with primary central nervous system lymphoma (PCNSL), by examining clinical and multimodal imaging characteristics and comparing with symptomatic VRL. DESIGN: Retrospective cross-sectional study. METHODS: Patients with cytologically or molecularly confirmed VRL were included. Patients were classified into three groups: primary VRL (PVRL), symptomatic VRL associated with PCNSL (PCNSL-S), or asymptomatic VRL associated with PCNSL (PCNSL-AS). Data encompassing demographics, visual symptoms, visual acuity (VA), and imaging characteristics were collected. Cross-sectional analyses of quantitative and categorical variables among groups were performed with one-way ANOVA and multinomial linear regression analyses. RESULTS: The study included 104 eyes from 56 patients with VRL. Twenty-nine patients (52%) were diagnosed with PVRL, and 27 patients (48%) were diagnosed with VRL associated with PCNSL. Among these, 17 (63%) reported visual symptoms (PCNSL-S), whereas 10 (37%) were asymptomatic (PCNSL-AS). PCNSL-AS patients exhibited better VA than PVRL patients (0.11 vs 0.76 LogMAR, P = 0.04) and distinct clinical features, with lower rates of anterior segment involvement (odds ratio [OR] = 0.02; 95% confidence interval [CI] 0.12-0.84; P < .01) and vitritis (OR = 0.32; 95% CI 0.11-0.91; P = .03). Subretinal infiltration was less common in PCNSL-AS cases compared to PVRL (OR = 0.14; 95% CI 0.02-1.11; P = 0.06) and PCNSL-S (OR: 0.08; 95% CI 0.01-0.69 P = 0.05) and was associated with worse VA (estimate = 0.55 LogMAR; 95% CI 0.29-0.8; P < .01). CONCLUSIONS: This study describes distinctive clinical and imaging features of asymptomatic VRL associated with PCNSL, characterized by better VA and less severe ocular involvement. The findings highlight the pivotal role of multimodal imaging in facilitating early detection of VRL in the staging of PCNSL. Future guidelines for PCNSL management should consider the necessity of diagnosing patients with asymptomatic VRL.

Gene therapy for Leber hereditary optic neuropathy.

INTRODUCTION: Leber hereditary optic neuropathy (LHON) is among the most frequent inherited mitochondrial disease, causing a severe visual impairment, mostly in young-adult males. The causative mtDNA variants (the three common are m.11778 G>A/MT-ND4, m.3460 G>A/MT-ND1, and m.14484T>C/MT-ND6) by affecting complex I impair oxidative phosphorylation in retinal ganglion cells, ultimately leading to irreversible cell death and consequent functional loss. The gene therapy based on allotopic expression of a wild-type transgene carried by adeno-associated viral vectors (AVV-based) appears a promising approach in mitochondrial disease and its efficacy has been explored in several large clinical trials. AREAS COVERED: The review work employed basic concepts in mitochondrial diseases, LHON, and gene therapy procedures. Reports from completed trials in LHON (i.e. RESCUE) were reviewed and critically compared. EXPERT OPINION: New challenges, as the improvement of the contralateral untreated eye or the apparently better outcome in patients treated in later stages (6-12 months), were highlighted by the latest gene therapy trials. A better understanding of the pathogenetic mechanisms of the disease together with combined therapy (medical and gene therapy) and optimization in genetic correction approaches could improve the visual outcome of treated eyes.

Quantitative Multimodal Imaging Characterization of Intraretinal Cysts versus Degenerative Pseudocysts in Neovascular Age-Related Macular Degeneration.

OBJECTIVE: To differentiate intraretinal fluid (IRF) cysts from degenerative pseudocysts in neovascular age-related macular degeneration (AMD) by quantitative multimodal imaging. DESIGN: Observational, cross-sectional. PARTICIPANTS: Patients affected by macular neovascularization secondary to AMD. METHODS: All patients were analyzed by OCT, OCT angiography (OCTA), and dense automatic real-time (ART) OCTA. New-onset cysts were considered IRF, whereas those cysts that were found to be persistent for at least 3 months were categorized as degenerative pseudocysts. Intraretinal cysts were automatically segmented to calculate cyst circularity. Peri-cyst space was quantitatively analyzed to assess the presence of perfusion signal and hyperreflective foci (HF). MAIN OUTCOME MEASURES: Best-corrected visual acuity, cyst circularity, peri-cyst perfusion, peri-cyst HF, fibrosis, and outer retinal atrophy. RESULTS: We analyzed 387 cysts collected from 35 eyes of 35 patients with neovascular AMD (14 men; mean age, 80 ± 5 years). We classified 302 IRF cysts and 85 degenerative pseudocysts. Intraretinal fluid cysts were characterized by significantly higher circularity (0.86; range, 0.81-0.91), perfusion signal in the peri-cyst space, and peri-cyst HF in 89% of cases (all P < 0.05). Degenerative pseudocysts showed significantly lower circularity (0.68; range, 0.64-0.76), no perfusion signal in the peri-cyst space, and peri-cyst HF in only 29% of cases (all P < 0.05). The adopted quantitative metrics significantly correlated with disease duration, number of injections, fibrosis, and outer retinal atrophy. CONCLUSIONS: Intraretinal fluid cysts can be discriminated from degenerative pseudocysts using a quantitative multimodal imaging approach. These findings are clinically relevant and should be included in future training models for artificial intelligence algorithms to improve the diagnostic power and fluid monitoring in neovascular AMD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Quantitative Optical Coherence Tomography Detection of New Neovascular Branches and Association With Exudation Recurrence in Neovascular Age-Related Macular Degeneration.

Purpose: The purpose of this study was to investigate the clinical role of multi-signal quantitative optical coherence tomography angiography (OCTA) perfusion sampling in neovascular age-related macular degeneration (AMD). Methods: The study was designed as a cross-sectional case series. We collected data from already treated macular neovascularization (MNV), characterized by (I) clinically relevant recurrent exudation, (II) nonclinically relevant recurrent exudation, and (III) inactive lesion. We proposed a new OCTA metric, calculating the gap between high-resolution (HR) and high-speed (HS) OCTA samplings, hypothesizing that this gap might improve the detection of new secondary MNV branches, being also associated with exudation recurrence. Main outcome measures were the HR-HS gap-based categorization of MNV lesions and the assessment of its association with exudative, minimally exudative, and inactive lesions. Results: Our cohort (which consisted of 32 MNV eyes; 32 patients; mean disease duration 5 years) was classified as type 1 (17; 53%), type 2 (11; 34%), or mixed type (4; 13%) MNV. Subretinal fibrosis was found in 17 out of 32 eyes (53%), whereas outer retinal atrophy involved 22 of 32 eyes (69%). HR-HS MNV gap was significantly different among MNV subgroups: 18% for the exudative subgroup, 12% for the minimally exudative subgroup, and 4% for the inactive subgroup. HR-HS gap significantly correlated with best corrected visual acuity (BCVA), disease duration, fibrosis, and outer retinal atrophy. Conclusions: HR-HS gap is a novel quantitative metric to detect the secondary novel branches of AMD-related MNV. This parameter is clinically relevant because it is associated with fluid recurrence. The integration of HR-HS gap in artificial intelligence models might help to predict MNV reactivation and to optimize treatment strategies.

Unusual presentation of ocular surface squamous neoplasia in a young healthy patient: A case report.

PURPOSE: To report an unusual case of ocular surface squamous neoplasia (OSSN) associated with human papilloma virus (HPV)-16 infection with an atypical morphology in a young otherwise healthy patient. CASE DESCRIPTION: A 17 year-old healthy male was referred to our department for evaluation of a corneal infiltrate with anterior stromal neovascularization in the right eye. One year before, the patient underwent an excision of a corneo-conjunctival lesion that was located inferiorly in the same eye. Histopathological analysis had shown moderate and severe dysplasia of the conjunctival epithelium and resulted positive for HPV-16. We performed a diagnostic incisional biopsy of the limbal conjunctiva and of the corneal epithelium for histological examination and molecular testing for HPV and Chlamydia by using polymerase chain reaction (PCR). Histopathologic evaluation demonstrated low-grade dysplasia of conjunctiva. PCR testing of the corneal epithelium was positive for HPV-16, similarly to the first biopsy performed by another centre. The patient was successfully treated with topical interferon alfa-2b (1,000,000 IU/ml) for a total of six months. After the treatment, the corneal infiltrate improved dramatically with regression of neovascularization and improvement of corneal transparency and vision. DISCUSSION: The present report described an atypical presentation of HPV-related OSSN due to its unusual morphology, young age of onset and absence of associated comorbidity. CONCLUSION: Conservative treatment with topical interferon-alpha 2b could be used to treat successfully HPV-16 positive OSSN, with no corneal irregularity or potential loss of vision compared to surgical excision.

Unraveling the Spectrum of Uveitis: Insights from an Epidemiological Study in a National Referral Center in Northern Italy.

PURPOSE: Uveitis embraces a heterogeneous group of vision-threatening inflammatory conditions. Understanding uveitis epidemiology, etiology, and clinical findings is fundamental for a prompt diagnosis and optimal patient management. The aim of the study is to report the epidemiology of uveitis in a national referral center in Northern Italy and investigate the visual prognosis. METHODS: This retrospective study was conducted at Uveitis Service (Ospedale San Raffaele) between June 2016 and May 2023. Demographic data, clinical characteristics, and etiological diagnoses of uveitis patients were collected, and visual prognosis was longitudinally explored. RESULTS: 1105 patients with uveitis were included in the study, while 47 patients presented neoplastic masquerade syndrome and have been excluded. The population had a slight majority of females (M/F ratio = 0.76), mean age was 47 years. 25% presented infectious uveitis, primarily due to herpetic etiology, toxoplasmosis, and tuberculosis. Non-infectious uveitis was the most prevalent diagnosis (38%), with sarcoidosis, HLA-B27-associated uveitis, and Fuch's uveitis as prominent causes. Anatomically, anterior segment was most frequently involved (41%). Significant improvement in visual acuity was observed at follow-up, particularly in patients with infectious uveitis. CONCLUSIONS: Our study sheds light into the epidemiological landscape of uveitis in Northern Italy, reflecting changing patterns due to factors such as migration and changing sexual habits. In particular, higher percentages of syphilis have been observed, compared to other European reports. The distribution of non-infectious uveitis reflects other epidemiological European series. Higher percentages of neoplastic masquerade syndromes support the need of early recognition. Our findings offer precious insights for uveitis epidemiology and daily clinical practice.

Optical coherence tomography (OCT) and OCT-angiography in syndromic versus non-syndromic USH2A-associated retinopathy.

PURPOSE: To compare non-syndromic and syndromic forms of USH2A-related retinitis pigmentosa (RP) by means of structural optical coherence tomography (OCT) and OCT-angiography (OCTA). METHODS: Observational, cross-sectional, multicenter study. All patients underwent best corrected visual acuity (BCVA) measurement, OCT (Spectralis HRA + OCT, Heidelberg Engineering) and OCTA (OCT DRI Topcon Triton, Topcon Corporation). We compared subfoveal choroidal thickness (SCT), choroidal vascularity index (CVI), presence of cystroid macular edema (CME), macular vessel density (VD) at the superficial and deep capillary plexa, as well as VD of the radial peripapillary capillary (RPC) network, between syndromic and non-syndromic patients with USH2A-associated retinopathy. RESULTS: Thirty-four eyes from 18 patients (7 females) were included. Thirteen patients (72.2%) were affected by Usher syndrome type 2, whereas the remaining 5 subjects (27.8%) had non-syndromic retinitis pigmentosa (nsRP). Syndromic patients were younger than nsRP (p = 0.01) and had a worse visual acuity than those with the exclusively retinal phenotype. Patients with Usher syndrome type 2 had a higher prevalence of CME and a thicker choroid compared to nsRP, although these results were not statistically significant (p = 0.775 and p = 0.122, respectively). Similarly, none of the other quantitative OCT and OCTA parameters was statistically different between the two groups. CONCLUSIONS: Despite their younger age, patients with Usher syndrome type 2 displayed similar choroidal and microvascular changes compared to those with nsRP.

Multimodal Imaging of Vitreo-Retinal Lymphoma: A Comprehensive Review.

PURPOSE: Vitreoretinal lymphoma (VRL) is a rare lymphoma affecting the vitreous and the retina. Clinical diagnosis is challenging and often delayed and may lead to aggravated prognosis. This study aims to review multimodal imaging findings in VRL. METHODS: We performed a comprehensive narrative review of the multimodal imaging findings that might be useful in the detection of VRL lesions. RESULTS: The most frequent ocular manifestations of VRL are vitritis, and retinal and sub-retinal Pigmented Epithelium (RPE) infiltrations. Color Fundus Photography (CFP) detects vitreous haze, optic nerve, retinal and sub-RPE infiltration. Ultra-wide field imaging allows visualization of different patterns of vitreous haze and monitoring of VRL evolution through the detection of chorio-retinal atrophy (CRA). Fundus Autofluorescence shows granular hypo- and hyper-autofluorescent pattern. Optical Coherence Tomography (OCT) reveals vitreous cells, vertical hyper-reflective lesions and sub-RPE infiltrates. Fluorescein Angiography (FA) shows hypo or hyperfluorescent round lesions at the late stages of the examination, while Indocyanine Green Angiography (ICGA) detects round areas of focal hypo-fluorescence in the early phases that gradually enlarge in the late phases. B-scan ultrasonography detects vitreous opacities and homogeneous hyperreflective corpuscular material in the vitreous, and is a strongly recommended tool in suspecting VRL and is particularly useful when vitreous haze is impeding retinal examination. CONCLUSION: Diagnostic vitrectomy with cytopathological analysis remains the gold standard for VRL diagnosis, however multimodal imaging allows the identification of suggestive retinal and vitreal lesions for early suspicion, diagnosis, and treatment and monitoring disease progression and response to treatment.

Clinical and Imaging Biomarkers Associated with Outer Retinal Atrophy Onset in Exudative Age-Related Macular Degeneration: A Real-Word Prospective Study.

INTRODUCTION: Macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) is well managed by anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections. However, outer retinal atrophy represents an unavoidable occurrence detected during follow-up. Several imaging metrics have been proposed as clinically relevant in stratifying the risk of onset of outer retinal atrophy. The main goal of this study is to evaluate the impact of noninvasive imaging metrics on the assessment of outer retinal atrophy onset in a large cohort of eyes with neovascular AMD managed in a real-world setting. METHODS: This study was a prospective, observational, case series. We included patients affected by newly diagnosed neovascular AMD, requiring anti-VEGF intravitreal injections. We collected clinical and imaging data, with a planned follow-up of 24 months. The multimodal imaging protocol included optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. We collected noninvasive imaging metrics and we assessed the relationship with the morphological and functional outcome evaluated at 12-month and 24-month time points. RESULTS: We included 370 eyes of 370 patients with exudative AMD (210 male; mean age 79 ± 8 years). MNV were classified as follows: type 1, 198 (54%); type 2, 89 (24%); polypoidal choroidal vasculopathy, 29 (7%); and type 3, 54 (15%). A total of 120 out of 370 eyes (33%) showed complete outer retinal atrophy at the end of the 2-year follow-up. The presence of intraretinal fluid, thinning of the Sattler choroidal layer, late anti-VEGF switch, the overall number of anti-VEGF injections, and the perfusion characteristics of the MNV were found to be the most relevant factors associated with the onset of outer retinal atrophy. The other collected metrics were found to be less clinically relevant, also showing no cumulative effect in the multivariate analysis (p > 0.05). CONCLUSIONS: We identified imaging metrics significantly associated with the 2-year risk onset of outer retinal atrophy. These metrics might pave the way for the development of future customized anti-VEGF treatment strategies.

Global experience of faricimab in clinical settings - a review.

INTRODUCTION: Faricimab is a bispecific antibody that acts to reduce neoangiogenesis in exudative retinal vascular disorders. It is approved for use in neovascular age-related macular degeneration and diabetic macular edema. We review the published efficacy and safety of faricimab in clinical settings. AREAS COVERED: A comprehensive literature review was conducted. Based on the 14 published real-world studies, 1127 patients (1204 eyes) were treated with faricimab. The majority of studies (14) included pre-treated patients. Most studies (13) showed central macular thickness improvement. However visual acuity improved in only half of the studies analyzed. Four studies demonstrated an extension of the treatment. Only 4 eyes (0.33%) reported intraocular inflammation and 3 eyes (0.24%) reported retinal pigment epithelial tear. EXPERT OPINION: The clinical experience with faricimab to date has the potential to provide a stable visual outcome with reduced treatment burden in cases that are resistant to other approved anti-VEGF agents. There are no major safety concerns based on this data analysis.

Real-world experience with fluocinolone acetonide intravitreal implant in patients with diabetic macular edema.

OBJECTIVES: to evaluate long-term effectiveness and safety of fluocinolone acetonide (FAc) implant used as second-line treatment in patients with persistent diabetic macular edema (DME). METHODS: retrospective data chart review of 241 pseudophakic eyes of 178 patients treated with FAc from July 2017 to December 2021 in 10 medical retinal units in Italy. The primary endpoint was the change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 2 years. A Student's paired t-test was used. Additional therapies for DME and intraocular pressure (IOP)-related events were also evaluated. RESULTS: efficacy of FAc was assessed in a subset of 111 eyes with at least 24 months of follow-up. Mean BCVA increased at 2 years by 5.1 ETDRS letters (95%CI = 2.6-7.5; p < 0.001) while mean CMT decreased by 189 µm (95% CI 151-227; p < 0.001). Thirty-eight of these eyes (34.2%) needed additional intravitreal treatments, mainly anti-VEGF. Safety was evaluated on the entire cohort of 241 eyes treated with FAc. Overall, 66 eyes (27.4%) required emergent IOP-lowering medications (typically within the first-year post FAc) while 14 eyes (5.8%) underwent trabeculectomy, mostly during the second year of follow-up. CONCLUSION: FAc implant provides a substantial long-term functional and anatomical benefit when used as second-line treatment in eyes with DME. IOP rise can be adequately managed with topical agents although some eyes may require IOP-lowering surgery.

Relationship of Topographic Distribution of Macular Atrophy Secondary to Neovascular AMD and Reading Performance.

Purpose: The purpose of this study was to provide a topographical assessment of macular atrophy in successfully treated neovascular age-related macular degeneration (AMD) eyes to investigate determinants of monocular reading performance. Methods: A total of 60 participants (60 eyes) with previously treated neovascular AMD and absence of optical coherence tomography (OCT) signs of exudation were enrolled. Reading performance was assessed monocularly using Radner charts. The following variables were obtained: (i) the reading acuity was defined as the logarithm of the reading acuity determination (LogRAD), at the smallest sentence, a patient is able to read in less than 30 seconds; (ii) the maximum reading speed was defined as the fastest time achieved and is calculated in words per minute (wpm). OCT images were reviewed for the presence of macular atrophy within the central, 4 inner and 4 outer Early Treatment Diabetic Retinopathy Study (ETDRS) grid subfields. Contributory factors affecting reading performance were examined using univariable and multivariable linear mixed model considering reading acuity and reading speed as dependent variables. Results: Median (interquartile range [IQR]) values were 0.53 (IQR = 0.17) LogRAD for reading acuity, and 144 (60) wpm for maximum reading speed. Thirty-five out of 60 (58.3%) eyes were characterized by the presence of macular atrophy. In multiple regression analysis, reading acuity was significantly associated with presence of macular atrophy in the foveal central circle (P = 0.024). Conversely, the maximum reading speed was associated with presence of macular atrophy in the inner-right ETDRS subfield (P = 0.005). Conclusions: We showed a significant relationship between presence and location of macular atrophy and reading performance in neovascular AMD.

Deep-learning based automated quantification of critical optical coherence tomography features in neovascular age-related macular degeneration.

PURPOSE: To validate a deep learning algorithm for automated intraretinal fluid (IRF), subretinal fluid (SRF) and neovascular pigment epithelium detachment (nPED) segmentations in neovascular age-related macular degeneration (nAMD). METHODS: In this IRB-approved study, optical coherence tomography (OCT) data from 50 patients (50 eyes) with exudative nAMD were retrospectively analysed. Two models, A1 and A2, were created based on gradings from two masked readers, R1 and R2. Area under the curve (AUC) values gauged detection performance, and quantification between readers and models was evaluated using Dice and correlation (R2) coefficients. RESULTS: The deep learning-based algorithms had high accuracies for all fluid types between all models and readers: per B-scan IRF AUCs were 0.953, 0.932, 0.990, 0.942 for comparisons A1-R1, A1-R2, A2-R1 and A2-R2, respectively; SRF AUCs were 0.984, 0.974, 0.987, 0.979; and nPED AUCs were 0.963, 0.969, 0.961 and 0.966. Similarly, the R2 coefficients for IRF were 0.973, 0.974, 0.889 and 0.973; SRF were 0.928, 0.964, 0.965 and 0.998; and nPED were 0.908, 0.952, 0.839 and 0.905. The Dice coefficients for IRF averaged 0.702, 0.667, 0.649 and 0.631; for SRF were 0.699, 0.651, 0.692 and 0.701; and for nPED were 0.636, 0.703, 0.719 and 0.775. In an inter-observer comparison between manual readers R1 and R2, the R2 coefficient was 0.968 for IRF, 0.960 for SRF, and 0.906 for nPED, with Dice coefficients of 0.692, 0.660 and 0.784 for the same features. CONCLUSIONS: Our deep learning-based method applied on nAMD can segment critical OCT features with performance akin to manual grading.

A Brazilian case of exudative perifoveal vascular anomalous complex responsive to aflibercept intravitreal injections.

PURPOSE: To report a case of exudative perifoveal exudative vascular anomalous complex (ePVAC) in a Brazilian healthy patient that underwent a complete resolution after aflibercept intravitreal injections. CASE DESCRIPTION: A 41-year-old healthy Brazilian man complained of acute central vision loss in his right eye (RE). Fundus examination showed a perifoveal hemorrhagic aneurysmal lesion, accompanied by several hard exudates in RE. On fluorescein angiography, these abnormalities showed a progressive hyperfluorescence with surrounding leakage. Optical coherence tomography (OCT) revealed a deep, perifoveal hyporeflective cystic space with a hyperreflective wall and hyperreflective material inside of fibrin-like aspect. Around this aneurism, intraretinal hyporeflective spaces suggestive of exudation were detected. Nor pathological flow signal, or telangiectatic dilations were evidenced on OCT-angiography. Therefore, a diagnosis of exudative ePVAC in RE was hypothesized. After an initial observation, the patient underwent three monthly aflibercept intravitreal injections (0.05 ml/2 mg), with a significative anatomical and functional improvement after two weeks from first dose. On last follow-up at five months from baseline, patient experienced no evidence of new exudation and a stable visual acuity. DISCUSSION: Placental growth factor (PlGF) may impact on pericytes' dropout, and thus on ePVAC development. In contrast to the other anti-VEGF drugs, aflibercept is the only molecule contrasting PlGF. Therefore, aflibercept would act on ePVAC not as an anti-VEGF drug, but rather as an anti-PlGF one. CONCLUSION: This report encouraged the use of aflibercept as a therapeutic option for ePVAC. Further studies are required to confirm our result and the impact of PlGF on ePVAC pathogenesis.

Rate and associations of inner retinal thinning in eyes with retinal vein occlusion and regressed macular oedema.

PURPOSE: To investigate the associations between visual acuity (VA) and structural optical coherence tomography (OCT) features in retinal vein occlusion (RVO) eyes after cystoid macular oedema (CMO) regression and to assess whether inner retinal thinning is progressive. METHODS: Retrospective observational study of RVO eyes with regressed CMO for at least 6 months. OCT scans at CMO regression were analysed, and features were correlated with VA at that visit. The inner retinal thickness was longitudinally compared between RVO and unaffected fellow eyes (controls) with linear mixed models. The rate of inner retinal thinning was obtained as the interaction term between disease status and time. Associations between inner retinal thinning and clinical characteristics were explored. RESULTS: Thirty-six RVO eyes were followed for 34.2 ± 21.1 months after CMO regression. The presence of ellipsoid zone disruption (regression estimate[standard error(SE)] = 0.16[0.04] LogMAR vs. intact, p < 0.001) and lower inner retinal thickness (regression estimate[SE] = -0.25[0.12] LogMAR for 100-µm increase, p = 0.01) were associated with worse VA. The inner retinal thickness decreased faster in RVO than controls (rate of retinal thinning -0.27 ± 0.09 µm/month vs. -0.08 ± 0.11 µm/month, p = 0.01). Macular ischaemia was associated with a faster rate of retinal thinning (interaction term macular ischaemia*follow-up time, p = 0.04). CONCLUSION: Inner retinal and photoreceptors' layers integrity are associated with better visual acuity once CMO resolves. RVO eyes undergo progressive inner retinal thinning after CMO regression, faster in eyes with macular ischaemia.

Endogenous Endophthalmitis Secondary to Infected Cutaneous Basal Cell Carcinoma: A Case Report.

INTRODUCTION: Endogenous endophthalmitis (EE) is a severe intraocular infection due to hematogenous spread of bacteria from an extraocular site. Recognition of the primary source of hematogenous spread of bacteria is essential to establish an adequate therapy and avoid other major complications. Infected cutaneous tumor has never been reported as a possible source of EE. PURPOSE: To describe the first case of EE due to hematogenous spread of methicillin-sensitive Staphylococcus aureus from an infected cutaneous basal cell carcinoma. Systemic antibiotic therapy and surgical excision of the cutaneous lesion were performed. CONCLUSION: Severe and long-standing skin infections should be considered as a rare cause of EE.

Non-vasogenic cystoid maculopathy in autosomal recessive bestrophinopathy: novel insights from NIR-FAF and OCTA imaging.

BACKGROUND: Autosomal Recessive Bestrophinopathy (ARB) is an inherited retinal disease caused by biallelic mutations in the BEST1 gene. Herein, we report the multimodal imaging findings of ARB presenting with cystoid maculopathy and investigate the short-term response to combined systemic and topical carbonic anhydrase inhibitors (CAIs). MATERIAL AND METHODS: An observational, prospective, case series on two siblings affected by ARB is presented. Patients underwent genetic testing and optical coherence tomography (OCT), blue-light fundus autofluorescence (BL-FAF), near-infrared fundus autofluorescence (NIR-FAF), fluorescein angiography (FA), MultiColor imaging, and OCT angiography (OCTA). RESULTS: Two male siblings, aged 22 and 16, affected by ARB resulting from c.598C>T, p.(Arg200*) and c.728C>A, p.(Ala243Glu) BEST1 compound heterozygous variants, presented with bilateral multifocal yellowish pigment deposits scattered through the posterior pole that corresponded to hyperautofluorescent deposits on BL-FAF. Vice versa, NIR-FAF mainly disclosed wide hypoautofluorescent areas in the macula. A cystoid maculopathy and shallow subretinal fluid were evident on structural OCT, albeit without evidence of dye leakage or pooling on FA. OCTA demonstrated disruption of the choriocapillaris throughout the posterior pole and sparing of intraretinal capillary plexuses. Six months of combined therapy with oral acetazolamide and topical brinzolamide resulted in limited clinical benefit. CONCLUSIONS: We reported two siblings affected by ARB, presenting as non-vasogenic cystoid maculopathy. Prominent alteration of NIR-FAF signal and concomitant choriocapillaris rarefaction on OCTA were noted in the macula. The limited short-term response to combined systemic and topical CAIs might be explained by the impairment of the RPE-CC complex.