Exploring Epigenetic Modifications as Potential Biomarkers and Therapeutic Targets in Glaucoma.

Glaucoma, a complex and multifactorial neurodegenerative disorder, is a leading cause of irreversible blindness worldwide. Despite significant advancements in our understanding of its pathogenesis and management, early diagnosis and effective treatment of glaucoma remain major clinical challenges. Epigenetic modifications, encompassing deoxyribonucleic acid (DNA) methylation, histone modifications, and non-coding RNAs, have emerged as critical regulators of gene expression and cellular processes. The aim of this comprehensive review focuses on the emerging field of epigenetics and its role in understanding the complex genetic and molecular mechanisms underlying glaucoma. The review will provide an overview of the pathophysiology of glaucoma, emphasizing the intricacies of intraocular pressure regulation, retinal ganglion cell dysfunction, and optic nerve damage. It explores how epigenetic modifications, such as DNA methylation and histone modifications, can influence gene expression, and how these mechanisms are implicated in glaucomatous neurodegeneration and contribute to glaucoma pathogenesis. The manuscript discusses evidence from both animal models and human studies, providing insights into the epigenetic alterations associated with glaucoma onset and progression. Additionally, it discusses the potential of using epigenetic modifications as diagnostic biomarkers and therapeutic targets for more personalized and targeted glaucoma treatment.

Intestinal microbiome: a new target for chalaziosis treatment in children?

Intestinal dysbiosis (changes in the gut commensal microbiome) is related to several ophthalmic diseases. The aim of this study was to verify whether oral specific probiotics can alter the clinical course of chalaziosis and its recurrence. A prospective comparative pilot study involving 26 children suffering from chalaziosis was conducted. Children were randomly divided into two groups. The first group received medical treatment (lid hygiene, warm compression and dexamethasone/tobramycin ointment for at least 20 days), and the second group received medical treatment plus a daily supplementation of oral probiotics (≥ 1 × 10^9 live cells of Streptococcus thermophilus ST10 (DSM 25246), ≥ 1 × 10^9 live cells of Lactococcus lactis LCC02 (DSM 29536) and ≥ 1 × 10^9 live cells of Lactobacillus delbrueckii subsp. bulgaricus (DSM 16606) with maltodextrin as the bulking agent (Probiotical S.p.A., Novara, Italy). All patients were evaluated at 2-week intervals for 3 months. If the lesion had not disappeared or decreased in size to 1 mm or less in diameter at the time of subsequent visits, the same procedure was repeated for another 3-month cycle. There was a significant difference in the time taken for complete resolution of the chalazion between the two groups in favour of the children receiving the probiotics. The treatment was not associated with any significant complications in either group. Trial registration: The trial was registered at clinical trials.gov under NCT04322500 on 25/03/2020 ("retrospectively registered").Conclusions: Modification of the intestinal microbiome with specific probiotics can alter the clinical course of chalaziosis in children by re-establishing intestinal and immune homeostasis. Probiotic supplementation can increase the effectiveness of traditional therapies by prompting the complete resolution of chalaziosis in a shorter amount of time, in an easy and feasible way. What is Known: • The intestinal microbiome plays a crucial role in several inflammatory diseases of the eye and is considered a therapeutic target. • Probiotics play a role in the prevention and treatment of different conditions in children. What is New: • In children probiotic supplementation is safe and effective. • Probiotic supplementation reduced the time required for complete resolution of the chalazion.

Ocular tropism of coronavirus (CoVs): a comparison of the interaction between the animal-to-human transmitted coronaviruses (SARS-CoV-1, SARS-CoV-2, MERS-CoV, CoV-229E, NL63, OC43, HKU1) and the eye.

PURPOSE: Several studies have reported conflicting results on ocular manifestations and transmission of coronavirus disease 2019 (COVID-19) whose causative virus, SARS-CoV-2, belongs to the coronavirus family, the seventh recognized as a human pathogen and the third causing a severe clinical syndrome. COVID-19 primarily affects the lungs, similar to the other human coronaviruses. Comparing the relation between the animal-to-human transmitted coronaviruses (SARS-CoV-1, SARS-Cov-2, MERS-CoV, CoV-229E, NL63, OC43, HKU1) and the eye may contribute to determining their actual eye-tissue tropism and risk of ocular transmission. METHODS: Literature review was conducted via Pubmed.gov, Google Scholar and medRixv using the following keywords: COVID-19, SARS-CoV-2, SARS-CoV-1, MERS-CoV, CoV-229E, NL63, OC43, HKU1, conjunctivitis, tear swab, ocular expression, ocular symptoms and human angiotensin converting enzyme-2 expression. Studies with lack in methodology were excluded. RESULTS: Sixteen observational studies were selected. The range for detection of viral RNA in tears was 0-8% for SARS-CoV-1 and 0-5.3% for SARS-CoV-2, while no reports were found for other coronaviruses. Ocular manifestations have been reported for NL63 and SARS-CoV-2. Ocular symptoms in the form of conjunctivitis/conjunctival congestion predominantly were detected in 65 (3.17%) out of 2048 reported patients with COVID-19 (range of 0.8-32%). Eye symptoms were not reported for the other coronaviruses. CONCLUSIONS: Data aggregation for coronaviruses shows a relatively low eye-tissue tropism. Conjunctival congestion is an uncommon manifestation of COVID-19 similar to all human coronaviruses' infections. In a low percentage of patients, the virus can be excreted in ocular fluids at different stages of the infection, regardless of positive SARS-Cov-2 throat swab. Albeit high viral loads in ocular tissue seem to have relatively low prevalence, the eye should be regarded as a potential source of infection dissemination for COVID-19.

Foveal Abnormality associated with epiretinal Tissue of medium reflectivity and Increased blue-light fundus Autofluorescence Signal (FATIAS).

PURPOSE: To describe a distinct vitreomacular interface disorder (VMID) termed Foveal Abnormality associated with epiretinal Tissue of medium reflectivity and Increased blue-light fundus Autofluorescence Signal (FATIAS). METHODS: A case series including forty-seven eyes of 47 patients. The included eyes must present an irregular foveal contour on optical coherence tomography (OCT) and a pathologically increased autofluorescent signal at the fovea on blue-light fundus autofluorescence (B-FAF). Main outcome measures were morphologic characteristics of the lesions, logarithm of minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), and central foveal thickness (CFT). RESULTS: The following two types of FATIAS were identified: (1) the step type characterized by an asymmetric contour of the foveal pit and by a tissue of medium reflectivity on the foveal surface and (2) the rail type characterized by a shallow foveal pit and a rail of tissue of medium reflectivity on the foveal surface. The outer retinal bands were continuous in all cases. Both types presented with an area of increased B-FAF signal, usually bilobed in the step type and round and centered on the foveal pit in the rail type. LogMAR BCVA was 0.09 ± 0.1 and 0.1 ± 0.1 (P = 0.91), and CFT was 197.8 ± 9.7 and 202.2 ± 13.2 (P = 0.19) in the step and in the rail group, respectively. CONCLUSIONS: We describe a distinct VMID named FATIAS. Two types of FATIAS may be appreciated with SD-OCT and B-FAF analyses, the step and the rail type. Both are characterized by abnormal foveal contour and autofluorescence signal.

Lamellar macular holes in the eyes with pathological myopia.

PURPOSE: To study the natural history and morphologic characteristics of lamellar macular holes (LMHs) in the eyes with pathological myopia. METHODS: Retrospective observational case series of 44 eyes of 44 patients examined at a single institutional vitreoretinal practice. The included eyes must present an irregular foveal contour and schitic or cavitated lamellar separation of neurosensory retina on spectral-domain optical coherence tomography (SD-OCT) and an area of increased autofluorescence on blue fundus autofluorescence (B-FAF) to be included. Presence of retinoschisis and posterior staphyloma, posterior vitreous status, changes of logarithm of minimum angle of resolution best-corrected visual acuity (BCVA), and changes of morphologic characteristics were evaluated. RESULTS: The mean follow-up period was 50.1 ± 28.9 months; 75% of the enrolled patients were female. At baseline, a standard epiretinal membrane (ERM) was detected in 93.2%, lamellar hole-associated epiretinal proliferation (LHEP) in 75%, and concomitant ERM and LHEP in 68.2% of the eyes, respectively. Visual acuity did not correlate with LMH diameters but correlated with central foveal thickness (p < 0.001). During the follow-up, the morphologic and functional parameters studied were relatively stable/improved in 60% of the eyes independently from the associated epiretinal material. Four eyes evolved to full-thickness (FT) MHs whereas spontaneous improvement was observed in five cases. CONCLUSIONS: LMHs in highly myopic eyes are more prevalent in females, are frequently associated with ERM and LHEP, and show substantial stability of BCVA and the anatomic parameters evaluated with B-FAF and SD-OCT over years-long follow-up.

Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration.

Macular degenerations represent leading causes of central blindness or low vision in developed countries. Most of these severe visual disabilities are due to age-related macular degeneration (AMD) and pathologic myopia (PM), both of which are frequently complicated by subfoveal choroidal neovascularization (CNV). Photodynamic therapy with verteporfin (PDT-V) is still employed for CNV treatment in selected cases or in combined regimen. In Caucasian patients, the common polymorphism G185T of factor XIII-A gene (FXIII-A-G185T; rs5985) has been described as predictor of poor angiographic CNV responsiveness to PDT-V. Nevertheless, the prognostic implications of this pharmacogenetic determinant on long-term visual outcome after a PDT-V regimen have not been evaluated. We retrospectively selected Caucasian patients presenting with treatment-naive CNV and receiving standardized PDT-V protocol for two years. The study population included patients affected by subfoveal CNV secondary to AMD or PM. We assessed the correlations between the polymorphic allele T of FXIII-A-G185T and: (1) total number of photodynamic treatments; and (2) change in visual acuity from baseline to the end of the follow-up period. Considering a total study population of 412 patients with neovascular AMD or PM, the carriers of 185 T-allele of FXIII-A (GT or TT genotype) received a higher number of photodynamic treatments than patients without it (GG wild-type genotype) (p < 0.01; mean number of PDT-V: 5.51 vs. 3.76, respectively). Moreover, patients with 185 T-allele of FXIII-A had a more marked worsening of visual acuity at 24 months than those with the GG-185 wild genotype (p < 0.01; mean difference in logMAR visual acuity: 0.22 vs. 0.08, respectively). The present findings show that the G185T polymorphism of the FXIII-A gene is associated with significant differences in the long-term therapeutic outcomes of patients treated with standardized PDT-V protocol. The comprehensive appraisal of both anti-thrombophilic effects due to FXIII-A G185T variant and photo-thrombotic action of PDT-V toward CNV provides several clues about the rationale of this intriguing pharmacogenetic correlation. Further investigations are warranted to outline the appropriate paradigm for guiding PDT-V utilization in the course of the combined therapeutic protocol for neovascular macular degeneration.

Myopia onset and progression: can it be prevented?

Myopia is the commonest ocular abnormality and the high and growing prevalence of myopia, especially but not only in Asian populations, as well as its progressive nature in children, has contributed to a recent surge in interest. Such worldwide growing prevalence seems to be associated with increasing educational pressures, combined with life-style changes, which have reduced the time that children spend outdoors. Highly nearsighted people are at greater risk for several vision-threatening problems such as retinal detachments, choroidal neovascularization, cataracts and glaucoma, thus the potential benefits of interventions that can limit or prevent myopia progression would be of remarkable social impact. Our understanding of the regulatory processes that lead an eye to refractive errors is undoubtedly incomplete but has grown enormously in the last decades thanks to the animal studies, observational clinical studies, and randomized clinical trials recently published. In this review we assess the effects of several types of life-style and interventions, including outdoor activities, eye drops, undercorrection of myopia, multifocal spectacles, contact lenses, and refractive surgery on the onset and progression of nearsightedness.

Influence of Vitreous Cortex Remnants on Normal Retinal Anatomy in Eyes with Primary Rhegmatogenous Retinal Detachment.

PURPOSE: To investigate the influence of vitreous cortex remnants (VCRs) removal on normal retinal anatomy in eyes with rhegmatogenous retinal detachment (RRD). DESIGN: Prospective cohort study. SUBJECTS: Patients with primary RRD operated with pars plana vitrectomy (PPV). METHODS: Blue fundus autofluorescence and spectral-domain OCT were obtained preoperatively, and at 1 and 6 months after operation. MAIN OUTCOME MEASURES: Primary outcomes: rate of retinal displacement and outer retinal folds (ORFs) at 1 month after operation. SECONDARY OUTCOMES: continuity of the external limiting membrane (ELM) and ellipsoid zone (EZ), and the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) at 6 months after operation. RESULTS: One hundred three eyes were included. Intraoperatively, peripheral VCRs (pVCRs) were found in 42 eyes (40.8%) and successfully peeled off from ≥2 quadrants in 37 eyes. Macular VCRs (mVCRs) were detected in 37 (35.9%) and successfully peeled off in 29 eyes. At the end of operation 44.7% and 55.3% of the eyes were tamponaded with 20% sulfur hexafluoride gas and silicone oil 1000 centistokes, respectively. The only variable significantly associated with displacement was the use of gas tamponade versus silicone oil (P = 0.001), whereas no significant association was found between retinal displacement and pVCRs (P = 0.58) or number of quadrants from which pVCRs were peeled off (P = 0.39). At 1 month postoperatively, ORFs were globally detected in 24 eyes (23.3%). Regression analysis showed a direct correlation between ORFs and the intraoperative detection of mVCRs (P = 0.02) and an indirect correlation between ORFs and mVCRs peeling (P = 0.004). Macular VCRs peeling did not influence the continuity of ELM and EZ at the 6-month follow-up (FU). Intraoperative absence of mVCRs (P = 0.0016) and peeling of mVCRs (P = 0.003) were associated with logMAR BCVA ≤0.3 at the 6-month FU. CONCLUSIONS: Peeling of pVCRs did not seem to influence the rate of retinal displacement, whereas peeling of mVCRs was associated with a reduced risk of developing ORFs without detrimental effect on the continuity of ELM/EZ at 6-month FU. The patients without mVCRs detected intraoperatively, or who underwent mVCRs peeling during operation, showed a significantly better visual acuity at the 6-month FU. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Natural History and Surgical Outcomes of Lamellar Macular Holes.

PURPOSE: To assess the natural history and surgical outcomes of lamellar macular holes (LMHs). DESIGN: Retrospective and consecutive case series. SUBJECTS: Patients with LMHs from multiple tertiary care centers. METHODS: Clinical charts and OCT scans were reviewed. MAIN OUTCOME MEASURES: The visual acuity (VA) changes and the occurrence rate of full-thickness macular hole (FTMH) were studied in both groups. Within the operated group, factors associated with 6-month VA and development of FTMH were explored. RESULTS: One hundred seventy-eight eyes were included, of which 89 were monitored and 89 underwent surgery. In the observation group, the mean VA decreased from 0.25 ± 0.18 to 0.28 ± 0.18 logarithm of the minimum angle of resolution (logMAR; P = 0.13), with 14 eyes (15.7%) that lost ≥ 0.2 logMAR VA, after 45.7 ± 33.3 months. Nine eyes (10.1%) spontaneously developed an FTMH. In the operated group, the mean VA increased from 0.47 ± 0.23 to 0.35 ± 0.25 logMAR at 6 months (P < 0.001) and 0.36 ± 0.28 logMAR (P = 0.001) after 24.1 ± 30.1 months. By multivariate analysis, better baseline VA (P < 0.001), the presence of an epiretinal membrane (P = 0.03), and the peeling of the internal limiting membrane (ILM; P = 0.02), with a greater effect of ILM perihole sparing, were associated with a greater 6-month VA. Perihole epiretinal proliferation sparing was associated with a better postoperative VA by univariate analysis (P = 0.03), but this was not significant by multivariate analysis. Eight eyes (9.0%) developed a postoperative FTMH. Using Cox proportional hazard ratios [HRs], pseudophakia at baseline (HR, 0.06; 95% confidence interval [CI], 0.00-0.75; P = 0.03) and peeling of the ILM (HR, 0.05; 95% CI, 0.01-0.39; P = 0.004) were protective factors, while ellipsoid zone disruption (HR, 10.5; 95% CI, 1.04-105; P = 0.05) was associated with an increased risk of FTMH. CONCLUSION: Observed eyes with LMH experienced, on average, progressive VA loss. Patients with LMH and altered vision may benefit from surgery. Internal limiting membrane peeling, with perihole ILM sparing, represents a crucial step of the surgery associated with a greater VA and a lower risk of postoperative FTMH. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Aqueous humor levels of vascular endothelial growth factor and adiponectin in patients with type 2 diabetes before and after intravitreal bevacizumab injection.

To determine the levels of vascular endothelial growth factor (VEGF) and adiponectin (APN) in the aqueous humor of patients with type 2 diabetes before and after injection of bevacizumab (IVB). Twenty eyes of twenty consecutive patients with type 2 diabetes with PDR and clinically significant macular edema were enrolled in this study. Aqueous samples were collected at baseline and one month after IVB to evaluate VEGF and APN levels. Twenty age-matched patients undergoing cataract surgery were used as control. Best-corrected visual acuity (BCVA) and foveal thickness (FT) changes after IVB were also measured. Safety was assessed by recording the incidence of ocular and non-ocular adverse events. At baseline APN and VEGF levels were significantly lower in controls than in PDR patients (APN: 3.6 ± 1.1 vs 18.7 ± 4.5 ng/ml; VEGF: 22.6 ± 16.1 vs 146.2 ± 38.71 pg/ml). After IVB, both compounds significantly decreased. FT and BCVA at baseline were significantly different between controls and patients (FT: 215.6 ± 34.8 vs 532.7 ± 112.4 µm; BCVA: 23.6 ± 4.2 vs 18.4 ± 7.3 letters). After IVB a significant decrease of FT with a concomitant improvement of BCVA occurred. Neither ocular nor systemic adverse events were reported. Our findings demonstrate that patients with type 2 diabetes, PDR and macular edema show VEGF and APN levels in aqueous humor higher than those found in control subjects. IVB significantly reduced the levels of both compounds, which remained anyway at concentrations higher than those recorded in control subjects.

Pars plana vitrectomy for the repair of primary, inferior rhegmatogenous retinal detachment associated to inferior breaks. A comparison of a 25-gauge versus a 20-gauge system.

BACKGROUND: To compare anatomical, functional outcomes and complications of high-speed 25-gauge (G) pars plana vitrectomy (PPV) versus 20-G PPV for the management of primary inferior rhegmatogenous retinal detachment (RRD) associated to inferior breaks/holes. METHODS: Eighty-five eyes from 85 patients with a minimum follow-up of 3 months were retrospectively evaluated. Forty-one patients underwent 25-G and 44 patients underwent 20-G PPV. All patients underwent PPV with fluid-air exchange, sulfur hexafluoride (SF6) 20 % gas tamponade and laser or cryo retinopexy. RESULTS: The mean follow-up interval was 6.51(± 2.32) and 6.63 (± 2.58) months in the 25-G and 20-G groups respectively. Single-operation success rate was 92.7 % for the 25-G group and 81.8 % for the 20-G group (P = 0.24). Post-operative hypotony was observed in no case. Redetachment occurred in 3 eyes operated on with 25-G and in 8 eyes operated on with 20-G system. All retinas were attached at final follow-up. Logarithm of the minimum angle of resolution visual acuity significantly improved from 0.69 ± 0.76 to 0.33 ± 0.37 in the 25-G and from 0.47 ± 0.59 to 0.21 ± 0.28 in the 20-G group (P = 0.0007 and P < 0.0001 respectively). CONCLUSIONS: High-speed PPV and SF6 gas tamponade using either 25-G or 20-G PPV system, yields similar single operation anatomical success rates for the repair of uncomplicated, primary inferior RRDs associated to inferior breaks.

Vitreous mediators in retinal hypoxic diseases.

The causes of retinal hypoxia are many and varied. Under hypoxic conditions, a variety of soluble factors are secreted into the vitreous cavity including growth factors, cytokines, and chemokines. Cytokines, which usually serve as signals between neighboring cells, are involved in essentially every important biological process, including cell proliferation, inflammation, immunity, migration, fibrosis, tissue repair, and angiogenesis. Cytokines and chemokines are multifunctional mediators that can direct the recruitment of leukocytes to sites of inflammation, promote the process, enhance immune responses, and promote stem cell survival, development, and homeostasis. The modern particle-based flow cytometric analysis is more direct, stable and sensitive than the colorimetric readout of the conventional ELISA but, similar to ELISA, is influenced by vitreous hemorrhage, disruption of the blood-retina barrier, and high serum levels of a specific protein. Finding patterns in the expression of inflammatory cytokines specific to a particular disease can substantially contribute to the understanding of its basic mechanism and to the development of a targeted therapy.

Topical nonsteroidal anti-inflammatory drugs for macular edema.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy. We provide an updated review on the clinical use of NSAIDs for retinal diseases, with a focus on the potential future applications.

Short-time prone posturing is well-tolerated and reduces the rate of unintentional retinal displacement in elderly patients operated on for retinal detachment.

PURPOSE: To evaluate the feasibility, efficacy and safety of strict prone posturing taken for 2 hours after operation in preventing the occurrence of unintentional retinal displacement in elderly patients operated on for retinal detachment (RD). METHODS: Twenty patients aged 60 or more with diagnosis of macula-off RD were asked to keep a strict face-down posturing for 2 hours after vitrectomy and 20% sulfur hexafluoride tamponade. IOP was measured immediately before and after surgery and after the 2-hour posturing. A questionnaire was administered to each patient to evaluate the rate of discomfort experienced because of the face-down posturing. Unintentional displacement of the retina was assessed by evaluating the presence of retinal vessel printings on fundus autofluorescence images taken 4 weeks after operation. RESULTS: The 2-hour posturing was generally well-tolerated. A mild neck pain was the most common reported symptom. Only a few patients experienced moderate breath shortness while posturing and none had to break the posturing because of respiratory problems. Intraocular pressure (IOP) measured before operation (11.7 ± 2.6 mmHg) was significantly different from IOP recorded at the end of surgery (18.9 ± 4.9 mmHg) and from IOP measured 2 hours after surgery (16.8 ± 4.7 mmHg, P<0.05, Friedman test). IOPs measured immediately and 2 hours after surgery did not differ significantly. Fundus autofluorescence imaging showed RVPs in 7 eyes. CONCLUSIONS: This study shows that a 2-hour face-down posturing is effective in reducing the rate of retinal displacement in patients operated on for rhegmatogenous retinal detachment using vitrectomy and SF6 20%. A 2-hour face-down posturing is feasible for elderly patients and does not appear to cause unwanted, post-operative IOP raises.

Biomarkers of Vitreous Cortex Remnants in Eyes With Primary Rhegmatogenous Retinal Detachment.

Purpose: The purpose of this study was to identify pre-operative biomarkers of vitreous cortex remnants (VCRs) in eyes with rhegmatogenous retinal detachment (RRD). Methods: Prospective case series of 103 eyes treated with pars plana vitrectomy (PPV) to repair RRD. Pre-operatively, optical coherence tomography (OCT) and B-scan ultrasonography (US) were used to study the vitreo-retinal interface and vitreous cortex status. If detected during PPV, VCRs were removed. Images acquired pre-operatively were compared with intra-operative findings and with postoperative OCT images taken at 1, 3, and 6 months of follow-up. Multivariate regression analyses were performed to determine associations between VCRs and pre-operative variables. Results: The presence of VCRs at the macula (mVCRs) and at the periphery (pVCRs), was ascertained intra-operatively in 57.3% and 53.4% of the eyes, respectively. Pre-operatively, a preretinal hyper-reflective layer (PHL) and a saw-toothed aspect of the retinal surface (SRS) were identified with OCT in 73.8% and 66% of the eyes, respectively. US sections showed a vitreous cortex running close and parallel to the detached retina upon static and kinetic examination (the "lining sign") in 52.4% of the cases. Multivariate regression analyses showed an association between PHL and SRS and intra-operative evidence of mVCRs (P = 0.003 and < 0.0001, respectively) and between SRS and "lining sign" and pVCRs (P = 0.0006 and 0.04, respectively). Conclusions: PHL and SRS on OCT and the "lining sign" on US appear to be useful pre-operative biomarkers of the intra-operative presence of VCRs. Translational Relevance: Preoperative identification of VCRs biomarkers may help to plan the operating strategy in eyes with RRD.

Intravitreal Brolucizumab for Pachychoroid Neovasculopathy Associated With Chronic Central Serous Chorioretinopathy.

Purpose: To evaluate the anatomical and functional outcomes of intravitreal brolucizumab in eyes with chronic central serous chorioretinopathy complicated by pachychoroid neovasculopathy. Methods: Retrospective analysis of 34 eyes treated with intravitreal brolucizumab. Twenty-five eyes (73.5%) had been treated with other anti-vascular endothelial growth factor agents before switching to brolucizumab, whereas nine eyes were naïve. Outcome measures included the change of central foveal thickness and subfoveal choroidal thickness, evaluation of sub/intraretinal fluid on optical coherence tomography, and change in best-corrected visual acuity. Results: Before starting brolucizumab, 23 eyes showed subretinal fluid, 8 both subretinal and intraretinal fluid, and 3 intraretinal fluid only. At the last visit, 22 eyes (64.7%) showed complete reabsorption of both intraretinal and subretinal fluid, whereas subretinal fluid was still present in 8 eyes (23.5%), and both intraretinal and subretinal fluid in 4 eyes (11.8%). The mean number of brolucizumab injections required to achieve complete fluid reabsorption was 2.8 ± 1.8. central foveal thickness decreased from 317.8 ± 109.3 µm to 239.8 ± 74.8 µm (P = 0.0005) and subfoveal choroidal thickness decreased from 399.3 ± 86.2 µm to 355.5 ± 92.7 µm at the end of the follow-up period (P = 0.0008). The mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.4 ± 0.2 to 0.3 ± 0.2 at 1 month after the first injection and remained stable at the same values at the end of the follow-up period (P = 0.04). Conclusions: Intravitreal brolucizumab is effective for the treatment of naïve and recalcitrant pachychoroid neovasculopathy. Translational Relevance: Intravitreal brolucizumab may represent an option in patients with pachychoroid neovasculopathy complicating chronic central serous chorioretinopathy.

Biofeedback Training after Successful Inverted Internal Limiting Membrane (ILM)-Flap Technique for High Myopic Macular Hole.

BACKGROUND: Microperimetric biofeedback training improved visual acuity and fixation stability in patients who previously underwent macular surgery. We aimed to compare the functional results of biofeedback training with the standard of care in patients who underwent successful inverted Internal Limiting Membrane (ILM)-flap technique for high myopic macular holes (hMMH). METHODS: This was a retrospective, comparative, cohort study. Patients with hMMH after surgical hole closure underwent microperimetric biofeedback using structured light stimulus plus acoustic tone (n = 12; Biofeedback) or standard of care with scheduled visits (n = 11; Control). Best-corrected visual acuity, retinal sensitivity at central 12° (RS) and 4° (CRS) with a mean deviation at central 12° (MD), and fixation stability as bivariate contour ellipse area (BCEA 68%, 95%, and 99%) were assessed at baseline and month 1, 3, 6, and 12. The Mann-Whitney test was used to test the difference between the groups. RESULTS: Baseline functional parameters were not significantly different among the groups. BCVA significantly improved in each group (Biofeedback, p = 0.002; Control, p ≤ 0.02) at all follow-up visits. CRS significantly improved at 6 (p = 0.03) and 12 (p = 0.01) months in the Biofeedback group and at month 12 (p = 0.01) in the Control group. RS (p = 0.001) and MD (p = 0.005) improved at the last follow-up only in the trained group. After training, BCEA 68% and 95% significantly improved (6 and 12 months, p < 0.05). The Biofeedback group had better results in RS (p ≤ 0.02), CRS (p ≤ 0.02), and BCEA 68%, 95%, and 99% (p ≤ 0.01) compared to the Control at all follow-ups. BCVA and MD were better in the Biofeedback group at month 3 (p = 0.01), and month 3 (p = 0.01) and 12 (p = 0.003), respectively. CONCLUSIONS: Microperimetric biofeedback can increase retinal sensitivity and stabilize fixation better than the standard care over months after a successful inverted ILM-flap for hMMH.

Microperimetric evaluation and predictive factors of visual recovery after successful inverted internal limiting membrane-flap technique for macular hole in high myopic eyes.

Introduction: Inverted Internal Limiting Membrane (ILM)-flap technique demonstrated its effectiveness, in terms of anatomical closure rate and visual acuity recovery for high myopic macular holes. We evaluated macular function after a successful inverted ILM-flap for macular holes in high myopic eyes (hMMH) using microperimetry to predict visual prognosis. Methods: A retrospective study on 23 eyes of 23 patients after surgical closure of hMMH, was performed. All patients underwent inverted ILM-flap and gas tamponade. Cataract surgery was performed in phakic eyes. Study outcomes including best-corrected visual acuity (BCVA), retinal sensitivity (RS) at central 12°, central retinal sensitivity (CRS) at central 4° and mean deviation (MD), and fixation behavior as bivariate contour ellipse area (BCEA, degrees2) measured by microperimetry, were evaluated over 6 months. A mixed-effects model was used to evaluate and compare the repeated measurements of outcomes between phakic and pseudophakic eyes. A regression model was performed to assess the relationship between BCVA at 6 months and independent variables. Results: Overall mean BCVA improved from 0.98 ± 0.21 logMAR at baseline to 0.47 ± 0.31 logMAR at the last follow-up (p < 0.001). Over 6 months, overall sensitivity measurements improved (RS, p = 0.001; CRS, p < 0.0001; MD, p = 0.03), and the BCEA decreased in dimension, although not significantly (p ≥ 0.05). The mixed model revealed a significantly better effect of inverted ILM-flap combined with cataract surgery on BCVA and CRS in phakic eyes than inverted ILM-flap alone in pseudophakic ones. The regression model revealed a relationship of 6-month BCVA with pre-operative BCVA (ß = 0.60, p = 0.02) and RS (ß = -0.03, p = 0.01). Conclusion: The inverted ILM-flap technique significantly improved visual acuity and retinal sensitivity after the hMMH closure, particularly when combined with cataract extraction. Pre-operative visual acuity and retinal sensitivity at central 12° may predict post-surgical visual acuity.

Intravitreal pegaptanib sodium (Macugen®) for treatment of diabetic macular oedema: a morphologic and functional study.

AIMS: To study whether morphologic (foveal thickness, FT) variations of clinically significant macular oedema (CMO) in patients suffering from diabetes following intravitreal pegaptanib sodium (IVP) injection were associated with functional [macular sensitivity (MS) and colour discrimination (CD)] changes. METHODS: A longitudinal, interventional, non-randomized study was performed. FT was assessed by optical coherence tomography (OCT), MS by microperimetry, best-corrected visual acuity (BCVA) by early treatment diabetic retinopathy study charts (ETDRS) and CD by Farnswoth-Munsell test. The treatment protocol consisted of three consecutive injections (0.3 mg/0.05 ml; baseline, week 6 and week 12). Follow-up checks were scheduled at 18, 24, 36 and 48 weeks, after injections. RESULTS: Thirty eyes of 30 patients with clinically significant CMO were included for analysis. After IVP a significant decrease of FT occurred with a mean reduction from baseline of 56.9% (P= 0.0001). An improvement of functional parameters was recorded in all patients (BCVA from 18.2 ± 8.5 letters to 25.5 ± 8.4 letters, P < 0.005, MS from 8.6 ± 2.16 dB to 10.6 ± 2.61 dB, P < 0.001, colour analysis from 376.1 ± 125.6 TES to 116 ± 34.6 TES, P= 0.0001). A statistically significant correlation between FT and BCVA as well as MS and CD was also found. Neither ocular nor systemic adverse events were reported. CONCLUSIONS: Intravitreal pegaptanib significantly reduced FT, with a concomitant improvement of MS and CD. This association emphasizes the efficacy of IVP in the treatment of CMO.

Early simultaneous fundus autofluorescence and optical coherence tomography features after pars plana vitrectomy for primary rhegmatogenous retinal detachment.

PURPOSE: To describe fundus autofluorescence and optical coherence tomography (OCT) features of the macula after pars plana vitrectomy for rhegmatogenous retinal detachment. METHODS: Thirty-three eyes of 33 consecutive patients with repaired rhegmatogenous retinal detachment with or without the involvement of the macula were prospectively investigated with simultaneous fundus autofluorescence and OCT imaging using the Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany) within a few weeks after the operation. RESULTS: Fundus autofluorescence imaging of the macula showed lines of increased and decreased autofluorescence in 19 cases (57.6%). On OCT, these lines corresponded to the following abnormalities: outer retinal folds, inner retinal folds, and skip reflectivity abnormalities of the photoreceptor inner segment/outer segment band. Other OCT findings, not related to abnormal lines on fundus autofluorescence, consisted of disruption of photoreceptor inner segment/outer segment band and collection of intraretinal or subretinal fluid. The presence of outer retinal folds significantly related to metamorphopsia but did not relate to poor postoperative visual acuity. CONCLUSION: Partial-thickness retinal folds occur commonly after vitrectomy for rhegmatogenous retinal detachment repair and may represent an important anatomical substrate for postoperative metamorphopsia. Fundus autofluorescence and OCT are both sensitive techniques for the detection of these abnormalities.