Uveal melanoma: Recent advances in immunotherapy.

Uveal melanoma (UM) is the most common primary intraocular cancer in adults. The incidence in Europe and the United States is 6-7 per million population per year. Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection, up to 50% of UM patients develop metastases that usually involve the liver and are fatal within 1 year. To date, chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM, which is still characterized by poor prognosis. No standard therapeutic approaches for its prevention or treatment have been established. The application of immunotherapy agents, such as immune checkpoint inhibitors that are effective in cutaneous melanoma, has shown limited effects in the treatment of ocular disease. This is due to UM's distinct genetics, natural history, and complex interaction with the immune system. Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations, UMs are usually triggered by a mutation in GNAQ or GNA11. As a result, more effective immunotherapeutic approaches, such as cancer vaccines, adoptive cell transfer, and other new molecules are currently being studied. In this review, we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.

Recent Developments in Gene Therapy for Neovascular Age-Related Macular Degeneration: A Review.

Age-related macular degeneration (AMD) is a complex and multifactorial disease and a leading cause of irreversible blindness in the elderly population. The anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionized the management and prognosis of neovascular AMD (nAMD) and is currently the standard of care for this disease. However, patients are required to receive repeated injections, imposing substantial social and economic burdens. The implementation of gene therapy methods to achieve sustained delivery of various therapeutic proteins holds the promise of a single treatment that could ameliorate the treatment challenges associated with chronic intravitreal therapy, and potentially improve visual outcomes. Several early-phase trials are currently underway, evaluating the safety and efficacy of gene therapy for nAMD; however, areas of controversy persist, including the therapeutic target, route of administration, and potential safety issues. In this review, we assess the evolution of gene therapy for nAMD and summarize several preclinical and early-stage clinical trials, exploring challenges and future directions.

Recent Advances of Adipose-Tissue-Derived Mesenchymal Stem Cell-Based Therapy for Retinal Diseases.

With the rapid development of stem cell research in modern times, stem cell-based therapy has opened a new era of tissue regeneration, becoming one of the most promising strategies for currently untreatable retinal diseases. Among the various sources of stem cells, adipose tissue-derived mesenchymal stem cells (ADSCs) have emerged as a promising therapeutic modality due to their characteristics and multiple functions, which include immunoregulation, anti-apoptosis of neurons, cytokine and growth factor secretion, and antioxidative activities. Studies have shown that ADSCs can facilitate the replacement of dying cells, promote tissue remodeling and regeneration, and support the survival and growth of retinal cells. Recent studies in this field have provided numerous experiments using different preclinical models. The aim of our review is to provide an overview of the therapeutic strategies, modern-day clinical trials, experimental models, and potential clinical use of this fascinating class of cells in addressing retinal disorders and diseases.

Innovative Strategies for Drug Delivery to the Ocular Posterior Segment.

Innovative and new drug delivery systems (DDSs) have recently been developed to vehicle treatments and drugs to the ocular posterior segment and the retina. New formulations and technological developments, such as nanotechnology, novel matrices, and non-traditional treatment strategies, open new perspectives in this field. The aim of this mini-review is to highlight promising strategies reported in the current literature based on innovative routes to overcome the anatomical and physiological barriers of the vitreoretinal structures. The paper also describes the challenges in finding appropriate and pertinent treatments that provide safety and efficacy and the problems related to patient compliance, acceptability, effectiveness, and sustained drug delivery. The clinical application of these experimental approaches can help pave the way for standardizing the use of DDSs in developing enhanced treatment strategies and personalized therapeutic options for ocular pathologies.

Optical Coherence Tomography-Based Choroidal Structural Analysis and Vascularity Index in Best Vitelliform Macular Dystrophy.

INTRODUCTION: This study investigated choroidal structural changes on optical coherence tomography (OCT) using choroidal vascularity index (CVI) and choroidal thickness (CT) in patients with Best vitelliform macular dystrophy (BVMD). METHODS: This retrospective case control study included 78 patients with BVMD of different clinical stages and 242 age- and gender-matched healthy controls. Subfoveal OCT scans were analysed. Total choroidal area (TCA), luminal area (LA) and CT were measured after image segmentation and binarization. CVI, a novel marker for choroidal angioarchitecture, was defined as the ratio of LA to TCA. CVI and CT were compared between BVMD and control group, as well as among the BVMD subgroups. RESULTS: Mean CVI was lower in eyes with BVMD (65.0 ± 3.5%) compared to that in control eyes (67.5 ± 3.9%) and this was statistically significant (p < 0.0001). There was no significant difference in subfoveal CT between BVMD (302.88 ± 81.68 µm) and control (309.31 ± 65.46 µm) eyes (p = 0.4799). In the subgroup analysis, all stages of BVMD showed lower CVI compared to control while SFCT remained similar. Within the BVMD subgroups, CVI and subfoveal CT did not differ significantly and both were not shown to be associated with visual acuity. CONCLUSION: Decreased CVI was shown in eyes with BVMD compared to control eyes, while no significant difference in subfoveal CT was seen. CVI may be helpful in the understanding of choroidal pathology in BVMD.

X-Linked Retinoschisis: Deep Phenotyping and Genetic Characterization.

PURPOSE: To examine the genetic and clinical features in children and adults with X-linked retinoschisis (XLRS). DESIGN: Single-center consecutive, retrospective, observational study. PARTICIPANTS: Adults and children with molecularly confirmed XLRS followed up between 1999 and 2020. METHODS: Analysis of genetic, clinical, and retinal imaging findings, including OCT and fundus autofluorescence (FAF), cross-sectionally and longitudinally, was performed. MAIN OUTCOMES MEASURES: RS1, variants, type of variants and phenotype correlations, age of onset, complications rates and types, fundoscopy findings, OCT metrics, FAF patterns, correlations including between best corrected visual acuity (BCVA) and age, and OCT characteristics. RESULTS: One hundred thirty-two male patients were identified harboring 66 retinoschisin 1 variants, with 7 being novel. The mean age at onset was 16.5 years (range, 0-58 years). Seventy-one patients (71/75 [94.7%]) were symptomatic at presentation; all had decreased best-corrected visual acuity (BCVA). Funduscopy findings were symmetric in 104 patients (104/108 [96.3%]), with the most common finding being macular schisis (82.4%), whereas peripheral retinoschisis was present in 38.9% and macular atrophy was present in 11.1%. Twenty patients (18.5%) demonstrated complications (vitreous hemorrhage, retinal detachment, or both). Mean BCVA was 0.65 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/89) in the right eye and 0.64 logMAR (Snellen equivalent, 20/87) in the left eye. Mean BCVA change over a mean interval of 6.7 years was 0.04 and 0.01 logMAR for right and left eyes, respectively. A normal FAF pattern was identified in 16 of 106 eyes (15.1%); 45 eyes (42.5%) showed a spoke-wheel pattern, 13 eyes (12.3%) showed foveal hyperautofluorescence, and 18 eyes (17.0%) showed a central reduction in signal. In total, 14 patients demonstrated evidence of progression on FAF over time. On OCT, foveoschisis was observed in 172 eyes (172/215 [80%]), parafoveal schisis was observed in 171 eyes (171/215 [79.5%]), and foveal atrophy was observed in 44 eyes (44/215 [20.5%]). Cystoid changes were localized to the inner nuclear layer (172/181 eyes [95%]), the outer nuclear layer (97/181 [53.6%]), and the ganglion cell layer (92/181 [50.8%]). Null variants were associated with worse final BCVA and aforementioned complications. CONCLUSIONS: X-linked retinoschisis is highly phenotypically variable, but with relative foveal and BCVA preservation until late adulthood, allowing more accurate prognostication. The slowly (often minimally) progressive disease course may pose a challenge in identification of early end points for therapeutic trials aimed at altering the kinetics of degeneration.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS BEFORE AND AFTER VITRECTOMY FOR MACULAR HOLES: Useful or Useless?

PURPOSE: To investigate the vascular remodeling of optical coherence tomography angiography in full-thickness macular hole surgery. METHODS: This retrospective, observational case series included 33 eyes of 33 patients with a full-thickness macular hole who underwent epiretinal membrane removal. Data were collected on best-corrected visual acuity, structural B-scan optical coherence tomography, and optical coherence tomography angiography preoperatively and at 1, 3, and 6 months postoperatively. Optical coherence tomography angiography was used to assess the retinal vascular density (VD) of the superficial vascular plexus and deep vascular plexus (DVP). Vascular density was assessed using the Early Treatment Diabetic Retinopathy Study grid for the whole, inner, and outer grids. RESULTS: A statistically significant correlation was found between the VD (whole, inner, and outer grids) of the superficial vascular plexus alone from baseline to 1-month postoperatively (P < 0.001). Similarly, VD was correlated from baseline to 1, 3, and 6 months postoperatively to the whole (P < 0.0005, F = 23.22), inner (P < 0.0005, F = 28.23), and outer Early Treatment Diabetic Retinopathy Study grids of DVP (P = 0.033, F = 3.49). The best-corrected visual acuity and VD were significantly correlated with the superficial vascular plexus and DVP at baseline and 6 months (P < 0.05, all correlations). The most significant correlation was observed at 6 months between best-corrected visual acuity and DVP in the whole, inner, and outer Early Treatment Diabetic Retinopathy Study grids (P < 0.001). CONCLUSION: Superficial vascular plexus and DVP are affected by full-thickness macular holes, with the most significant effects being on the DVP. Full-thickness macular hole surgery leads to an improvement in the best-corrected visual acuity in many eyes and the restoration of the VD, especially of the DVP.

The Role of OCT Angiography in the Assessment of Epiretinal Macular Membrane.

BACKGROUND: The aim of this observational study is to assess pre- and postoperative retinochoroidal vascular changes in patients undergoing epiretinal macular membrane (ERM) surgery by using optical coherence tomography angiography (OCTA). MATERIALS AND METHODS: 23 eyes affected by ERM and those which underwent phacovitrectomy associated with ERM peeling were enrolled. They were evaluated using structural OCT and OCTA before surgery and at 1, 3, and 6 months postoperatively. RESULTS: We found a statistically significant (p < 0.05) increase in the superficial capillary plexus vessel density (VD) from baseline to the 6-month follow-up. We observed a large increase in both the perfusion density (PD) and the VD of the deep capillary plexus between baseline and the 6-month follow-up (p < 0.001). A significant decrease in the VD and PD of the choriocapillaris (CC) from baseline to the 1st month and a significant increase in CC perfusion density at the 6-month follow-up compared to the preoperative value were revealed. The FAZ area and perimeter after surgery significantly increased during the follow-up (p < 0.001) at baseline retinal and choroidal plexi with a lower PD or VD correlated with worse visual acuity (p < 0.05 for all plexi). At baseline and at the 1-month follow-up, a significant correlation was found with the FAZ area and the FAZ perimeter: a smaller FAZ area or a smaller FAZ perimeter was correlated to a lower visual acuity. Before surgery, negative correlations (p < 0.05) were found between the Govetto ERM stages and perfusion density of the SCP and the DCP and between the Govetto stages and vessel density of the DCP. CONCLUSIONS: In our study, OCTA detected vascular alterations induced by the presence of the ERM, allowing several correlations with functional data. In these patients, OCTA may be useful to add new potential surgical prognostic factors.

Optical Coherence Tomography Angiography for the Evaluation of Retinal Vasculature in Fabry Disease: Our Experience and Review of Current Knowledge.

Purpose: Optical coherence tomography angiography (OCTA) is a non-invasive and objective tool for the evaluation of the retinal microvascular changes in Fabry disease (FD). We investigated changes in retinal vasculature in FD patients, and the possible correlation with systemic parameters, by using OCTA, and reviewed the current status of literature. Methods: Thirteen FD patients (eight females, five males, mean age 49.85 ± 14.7 years) were compared with 13 age- and sex-matched healthy controls. OCTA 3 × 3 mm macular scans were performed in all subjects. We evaluated the vessel density and vessel perfusion in distinct macular areas (whole, inner, and outer) of both the superficial capillary plexus (SCP VD and SCP VP) and of the deep capillary plexus (DCP VD and DCP VP). We also evaluated the foveal avascular zone (FAZ) metrics (area, perimeter, and circularity), and correlation between systemic and OCTA parameters. A literature review on the current understanding of OCTA in FD is then presented. Results: FD patients showed significantly lower SCP VD values in the whole area (17.37 ± 2.08 mm-1 vs. 18.54 ± 1.21 mm-1; p-value 0.022), as well as in the outer area (17.46 ± 2.10 mm-1 vs. 19.08 ± 1.14 mm-1; p-value 0.002), but not in the inner. Even the DCP VD was significantly lower in all the imaged areas: whole (17.75 ± 3.93 mm-1 vs. 19.71 ± 1.20 mm-1; p-value 0.024), outer (18.25 ± 4.17 mm-1 vs. 20.33 ± 1.20 mm-1; p-value 0.023), and inner (19.54 ± 4.17 mm-1 vs. 21.96 ± 1.55 mm-1; p-value 0.011). There were no significant differences in vessel perfusion parameters (both SCP VP and DCP VP ones) and FAZ. No significant correlations were found between the OCTA parameters and systemic parameters (maximal left ventricular wall thickness and glomerular filtration rate) in FD patients. Conclusions: OCTA can be considered as a promising non-invasive tool, which enables a quantitative evaluation of retinal vascular involvement in FD, despite the varying data reported in literature. Our results support the use of OCTA as an objective tool to evaluate retinal vascular abnormalities in FD. The utility of OCTA in FD needs to be validated by longitudinal studies taking into account the overall progression of the disease.

Adaptive Optics Imaging in Patients Affected by Pseudoxanthoma Elasticum.

PURPOSE: To describe the retinal findings of patients affected by pseudoxanthoma elasticum (PXE) using a multimodal imaging approach including flood-illumination adaptive optics ophthalmoscopy (AO). DESIGN: Retrospective case series. MATERIALS AND METHODS: Patients affected by PXE were retrospectively studied. Clinical data, color, infrared and autofluorescence fundus imaging, optical coherence tomographic scans, and AO examinations were collected. Furthermore, the photoreceptor count was assessed. PXE diagnosis was confirmed by a positive skin biopsy and/or genetic testing. RESULTS: Twenty-one eyes of 18 patients (11 females and 7 males) were included in the study. In 3 patients, both eyes were studied. The mean age at examination was 37.7 ± 16.4 years (range 14-66) and the mean best-corrected visual acuity (BCVA) was 0.1 ± 0.2 logMAR (range 0-1). We identified 3 types of angioid streaks (AS) using AO: "crack," "band," and "hypopigmented." The first 2 were very similar and they differed in size; the third type showed specific clinical features. Comet lesions appeared as hyper-reflective round lesions on AO imaging. In all eyes, the cone mosaic appeared reduced inside the streaks compared to the neighboring areas (13,532.8 ± 1,366.5 cones/mm2 vs 16,817.1 ± 1,263.0 cones/mm2 respectively). CONCLUSION: Using AO imaging in PXE-related retinopathy, we were able to observe the presence of the photoreceptors within the angioid streaks, differentiate 3 types of angioid streaks, based on size and reflective features, and identify the very small crystalline bodies not identifiable using other retinal imaging techniques.

Combining cataract surgery with 25-gauge high-speed pars plana vitrectomy: A prospective study.

PURPOSE: To compare visual outcome and postoperative complications of combined 25-gauge pars plana vitrectomy and phacoemulsification with vitrectomy alone surgery in patients with epiretinal membrane and macular hole. METHODS: A total of 110 eyes (73 eyes with epiretinal membrane and 37 eyes with macular hole) were enrolled in this prospective study. The eyes were divided into two groups: Group A included 55 eyes which underwent phacovitrectomy at the same time and Group B included 55 eyes which underwent vitrectomy alone. Follow-up visits were at 1, 3, and 6 months. RESULTS: The best-corrected visual acuity correlation by analysis of variance measurement showed statistically non-significant differences between the two groups (p = 0.32). The post hoc analysis from baseline, 1°, 2°, and 3° follow-ups was not statistically significant (p > 0.05). The most common postoperative complication was cystoid macular edema that has been detected in 11 patients (10%) (seven eyes in Group A and four eyes in Group B): 2 patients (1.8%) developed a chronic macular edema. Intraocular hypertension occurred in five eyes (4.5%) (three in Group A and two in Group B). Four eyes (3.6%) underwent another surgical procedure for a persistent macular hole (two in Group A and two in Group B). The intraocular lens repositioning was performed one day after surgery in three eyes (2.7%) (Group A). The mean preoperative visual acuity was not different between the two groups (p = 0.80). CONCLUSION: No significative differences between combined surgery and vitrectomy alone have been detected, in terms of postoperative complications and visual outcome.

HUMAN AMNIOTIC MEMBRANE TO TREAT MACULAR HOLES THAT FAILED TO CLOSE, SULFUR HEXAFLUORIDE ENDOTAMPONADE VERSUS AIR ENDOTAMPONADE: A Prospective Comparative Study.

BACKGROUND/PURPOSE: To determinate the efficacy of the human amniotic membrane plugs with sulfur hexafluoride versus human amniotic membrane plug with air as endotamponade to treat macular holes that failed to close after vitrectomy plus internal limiting membrane peeling. Multimodal imaging was focused to evaluate preoperative features and postoperative changes. METHODS: Prospective interventional comparative study. Twenty eyes of 20 patients affected with macular hole that failed to close were divided into 2 groups: 10 eyes received an amniotic membrane plug with 20% sulfur hexafluoride tamponade and 10 eyes received an amniotic membrane plug with air tamponade. All eyes were studied using multimodal advanced diagnostic tools, such as spectral-domain optical coherence tomography, optical coherence tomography angiography, microperimetry, and adaptive optics to investigate the postoperative results. RESULTS: In both groups, all macular holes were found successfully closed after 12 months. Mean preoperative best-corrected visual acuity was 20/400 in the SF6 group and 20/250 in air group. Final mean best-corrected visual acuity was 20/63 in both groups. The superficial capillary plexus, studied using optical coherence tomography angiography, showed a statistically significant difference between the treated and the fellow eyes. Adaptive optics images revealed the presence of a photoreceptor cell mosaic in the area of the amniotic membrane plug. CONCLUSION: The human amniotic membrane combined with air endotamponade demonstrated its effectiveness to seal macular holes that failed to close after vitrectomy plus internal limiting membrane peeling. Advanced multimodal diagnostic imaging helped us to better understand the modifications associated with the use of the amniotic membrane in these cases.

OCT Angiography Findings in Macula-ON and Macula-OFF Rhegmatogenous Retinal Detachment: A Prospective Study.

Background: The aim of the study was to evaluate pre-operative and post-operative retinal vasculature using optical coherence tomography angiography (OCTA) in patients who underwent rhegmatogenous retinal detachment (RRD) surgery repair. Materials and Methods: A total of 33 eyes were included in this prospective consecutive observational study: 15 affected by macula-ON and 18 by macula-OFF RRD. Superficial (SCP), deep capillary plexus (DCP), and foveal avascular zone (FAZ) area variations were evaluated by OCTA and correlated with visual acuity (VA) during a six-month follow-up. Results: In the macula-ON group, the preoperative vascular density (VD) of the whole SCP (wSCP) on affected eyes was lower than that of the fellow eyes (p < 0.05); this difference disappeared at 6 months after surgery (p = 0.88). The wSCP VD and the parafoveal SCP (pfSCP) VD increased during follow-up (p < 0.05); moreover, the higher the preoperative wSCP and pfSCP VD, the better the baseline VA (p < 0.05). In the macula-OFF group, at the first and sixth months after surgery, the larger the FAZ, the lower the VA (p < 0.05). Conclusions: Macula-ON SCP VD affected preoperative VA, and it was lower than the fellow eye, but recovered over time. In the macula-OFF group, a larger FAZ area was related to a worse VA, as is the case in diabetes and in retinal vein occlusion (RVO).

Intravitreal Dexamethasone Implant as a Sustained Release Drug Delivery Device for the Treatment of Ocular Diseases: A Comprehensive Review of the Literature.

Drug delivery into the vitreous chamber remains a great challenge in the pharmaceutical industry due to the complex anatomy and physiology of the eye. Intravitreal injection is the mainstream route of drug administration to the posterior segment of the eye. The purpose of this review is to assess the current literature about the widening use of the intravitreal 0.7 mg dexamethasone (Dex) implant, and to provide a comprehensive collection of all the ocular disorders that benefit from Dex administration. Although anti-vascular endothelial growth-factors (VEGFs) have been largely indicated as a first-choice level, the Dex implant represents an important treatment option, especially in selected cases, such as vitrectomized eyes or patients in whom anti-VEGF failed or are contraindicated. In this article, the safety profile as well as the list of the possible complications related to intravitreal Dex injection are also discussed.

Human Amniotic Membrane Plug to Restore Age-Related Macular Degeneration Photoreceptor Damage.

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of legal blindness in adults 65 years of age and older. Choroidal neovascularization (CNV) can complicate AMD and lead to severe visual acuity reduction. Despite the several treatments available, if the retinal pigment epithelium is damaged, we have to cope with the impossibility of restoring acceptable visual acuity using only medical treatments. DESIGN: Prospective, consecutive, interventional study. PARTICIPANTS: Eleven patients affected by AMD, 6 patients affected by CNV, and 5 patients affected by geographic atrophy. METHODS: All patients underwent a pars plana vitrectomy with subretinal implantation of human amniotic membrane (hAM) to induce photoreceptor regeneration and partial visual acuity restoration. MAIN OUTCOME MEASURES: Primary study outcome was visual acuity improvement. Secondary outcomes were multimodal imaging results. RESULTS: Mean preoperative best-corrected visual acuity (BCVA) was 20/2000 (2 logarithm of the minimum angle of resolution [logMAR]), and all the patients showed a BCVA of counting fingers or less. Mean final BCVA was 20/400 (1.31 logMAR), ranging from 20/2000 to 20/100 (2-0.7 logMAR). OCT angiography was used to measure retinal vascularization in the treated eye compared with the fellow eye. A high correlation between BCVA and deep vascular density was evidenced. Adaptive optics findings, obtained over the retinal area where the highest functionality was observed, were evaluated using microperimetry. The images showed possible photoreceptor presence over the hAM membrane. CONCLUSIONS: This work supports the feasibility and safety of the hAM to promote partial retinal function restoration 6 months after surgery with visual acuity improvement. The advanced diagnostics help to understand the interaction between the hAM and photoreceptors and suggest that photoreceptor regeneration may occur.

Choroidal Vascularity Index: An In-Depth Analysis of This Novel Optical Coherence Tomography Parameter.

Remarkable improvements in optical coherence tomography (OCT) technology have resulted in highly sophisticated, noninvasive machines allowing detailed and advanced morphological evaluation of all retinal and choroidal layers. Postproduction semiautomated imaging analysis with dedicated public-domain software allows precise quantitative analysis of binarized OCT images. In this regard, the choroidal vascularity index (CVI) is emerging as a new imaging tool for the measurement and analysis of the choroidal vascular system by quantifying both luminal and stromal choroidal components. Numerous reports have been published so far regarding CVI and its potential applications in healthy eyes as well as in the evaluation and management of several chorioretinal diseases. Current literature suggests that CVI has a lesser variability and is influenced by fewer physiologic factors as compared to choroidal thickness. It can be considered a relatively stable parameter for evaluating the changes in the choroidal vasculature. In this review, the principles and the applications of this advanced imaging modality for studying and understanding the contributing role of choroid in retinal and optic nerve diseases are discussed. Potential advances that may allow the widespread adoption of this tool in the routine clinical practice are also presented.

ATTENUATION OUTER RETINAL BANDS ON OPTICAL COHERENCE TOMOGRAPHY FOLLOWING MACULAR EDEMA: A Possible Manifestation of Photoreceptor Misalignment.

PURPOSE: Macular edema is a common retinal disease which may leave important anatomical and functional sequelaes. Directional fundus imaging consists of comparing on- and off-axis images to reveal angle-dependent reflectance properties of fundus structures, which may be related to misaligned photoreceptors. Here, we analyzed directional optical coherence tomography (OCT) and flood-illumination adaptive optics ophthalmoscopy images to detect evidence of misaligned photoreceptors following macular edema. METHODS: Transversal, observational study. Nine patients having recovered a normal macular profile after macular edema due to retinal vein occlusion were included. For each patient, a reference OCT scan (i.e., with the incident beam normal to the fovea) was acquired, and off-axis scans were then acquired by laterally shifting the entry pupil. In addition, in four of these eyes, directional adaptive optics ophthalmoscopy documented the directional variations of cone metrics. RESULTS: Included patients comprised two women and seven men (age range, 19-76 years). Reference OCT scans showed patchy attenuation of the cone outer segment tips and to a lesser extent of the inner segment/outer segment lines in all, but two eyes; these. Increased intensity of the cone outer segment tips and inner segment/outer segment lines could be observed on off-axis scans. Accordingly, fusion images showed 66% average reduction of the length of cone outer segment tips attenuation. In two cases, although reference scans showed continuity of outer bands, focal attenuation was evidenced in off-axis images. Directional adaptive optics ophthalmoscopy imaging showed a strong directional variability of cone counts in these areas, ranging from near absence to roughly two-third of reference values. In each case, directional variations of cone counts paralleled those of the reflectance of outer bands. CONCLUSION: After macular edema, focal attenuations of the inner segment/outer segment and of the cone outer segment tips lines may be present on OCT. These areas may show a strong directional variability by both OCT and adaptive optics ophthalmoscopy, suggesting that misaligned photoreceptor outer segments contribute to such features. The evaluation of outer retinal damage following macular edema should therefore take into account the optical Stiles-Crawford effect to disambiguate missing from misaligned cones.

Morpho-Functional Evaluation of Full-Thickness Macular Holes by the Integration of Optical Coherence Tomography Angiography and Microperimetry.

(1) Objective: To use optical coherence tomography angiography (OCTA) and microperimetry (MP) to evaluate the correlation between retinal structure and function in patients with idiopathic, full-thickness macular holes (FTMHs) (2) Methods: This prospective, observational study included 11 eyes of 10 patients with FTMHs evaluated before surgery using OCTA and MP. MP sensitivity maps were superimposed and registered on slabs corresponding to superficial capillary plexus (SCP) and deep capillary plexus (DCP) on OCTA, and on the outer plexiform layer (OPL) and the Henle fiber layer (HFL) complex in en face OCT. On these maps, mean retinal sensitivity was calculated at 2° and 4°, all centered on the FTMH. Cystic cavity extension was assessed on the slab corresponding to the OPL + HFL complex in en face OCT and DCP in OCTA using the Image J software (Version 1.49v; National Institutes of Health, Bethesda, MD, USA); (3) Results: Absolute scotomas were observed corresponding to the FTMH. Additionally, rings of relative scotoma in the perilesional area were detected and correlated to the cystic spaces on en face OCT and OCTA. There was a significant correlation between reduced retinal sensitivity at 2° and 4° diameters around the FTMH and the extension of cystic areas (p < 0.01). There was a significant correlation between the extension of cystic cavities and BCVA (p < 0.01). (4) Conclusions: Morpho-functional analysis of FTMH using OCTA and MP, and the correlation between vascular abnormalities and impaired retinal sensitivity, may provide new, useful information. This integrated evaluation of FTMH may be useful to determine the function-structure correlation before and after vitreoretinal surgery, in order to gain a better understanding of the functional consequences induced by the morphological alterations, assessing outcomes in a more objective way, and potentially adding new surgical prognostic factors.

A human Amniotic Membrane plug to manage high myopic macular hole associated with retinal detachment.

OBJECTIVE: To assess the efficacy of the human amniotic membrane (hAM) to treat (HMMH) associated with retinal detachment (RD). MATERIAL AND METHODS: Ten eyes of 10 patients with recurrent HMMH and RD, who had already undergone one or more pars plana vitrectomy (PPV), underwent a PPV with an hAM plug implanted in the macular hole. The initial five patients enrolled were tamponaded with (SO) while the subsequent five patients with 10% octafluoropropane (C3 F8 ). Silicon oil was removed in all five patients 2 months later. No statistical differences were reported between the two groups. RESULTS: Final retinal reattachment was achieved in all the patients. BCVA improved from 1.73 logMAR to 0.94 logMAR after 6 months. No adverse events were registered during follow-up. CONCLUSION: An hAM plug is an efficient substrate to manage HMMH associated with RD resulting in encouraging visual acuity recovery.