Search Results (186)

Background/Objectives: This study aimed to compare hematological and inflammatory markers among patients with dry and wet age-related macular degeneration (AMD) and healthy controls, and to evaluate the influence of geographic atrophy (GA) in dry AMD and treatment response (TR) in wet AMD on these markers. Methods: The study included patients with dry AMD (n = 54), wet AMD (n = 53), and age- and sex-matched controls (n = 55). Hematological parameters, serum albumin, and systemic inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune–inflammation index (SII), systemic inflammation response index (SIRI), pan-immune–inflammation value (PIV), and hemoglobin, albumin, lymphocyte, and platelet index (HALP), were compared among the groups. Results: Age and sex distributions did not differ significantly between groups. Compared to controls, the wet AMD group had significantly higher neutrophil counts (p = 0.013), red cell distribution width (RDW) (p = 0.033), and inflammatory indices, including NLR, PLR, SII, SIRI, and PIV (all p < 0.01). HALP levels were significantly lower in wet AMD (p < 0.001). Dry AMD patients also had higher PLR (p = 0.045) and RDW (p = 0.005) than controls. When comparing wet and dry AMD groups directly, SIRI (p = 0.041) and PIV (p = 0.029) were significantly elevated in wet AMD, indicating stronger systemic inflammatory burden. In the dry AMD subgroup, patients with GA had significantly lower hemoglobin (p = 0.002) and erythrocyte counts (p = 0.039) than those without GA. No significant differences were observed between TR-positive and TR-negative wet AMD patients. Conclusions: Patients with wet AMD exhibit a more pronounced systemic inflammatory profile than both dry AMD patients and healthy controls. These findings support the hypothesis that systemic inflammation may contribute to AMD pathogenesis. Geographic atrophy in dry AMD may also be associated with additional hematologic alterations, whereas treatment response in wet AMD is not reflected in systemic markers. Full article

Background/Objectives: Pachydrusen are a drusen subtype associated with the pachychoroid disease spectrum; however, their long-term natural history and pathophysiological significance remain unclear. We investigated 5-year morphological and topographic changes in pachydrusen using diagnostic criteria incorporating late-phase indocyanine green angiography (ICGA) hyperfluorescence. Methods: This retrospective observational study included fellow eyes with pachydrusen from patients with unilateral neovascular age-related macular degeneration. Pachydrusen were defined as sub-retinal pigment epithelium (RPE) deposits ≥ 125 µm in size with corresponding hyperfluorescence on late-phase ICGA. Lesion number, size, and spatial distribution (ETDRS grid and quadrant-based classification) were evaluated at baseline and 5 years. The incidence of macular neovascularization (MNV) and its colocalization with pachydrusen were assessed. Results: Among 57 fellow eyes with pachydrusen, incident MNV developed in 8 eyes (14.0%) during follow-up; the mean time to onset was 25.6 ± 16.3 months. No clear colocalization between pachydrusen and incident MNV was observed. Nineteen eyes completed the 5-year follow-up period. Pachydrusen were predominantly located outside the 6000 µm ETDRS grid at baseline (63.4%) and 5 years (66.3%), significantly exceeding the expected proportion based on the area ratio (p < 0.001). The lesions were most frequently observed in the superotemporal quadrant (52.6%). Over 5 years, 19.8% of the lesions increased in size, 67.2% remained stable, and 12.9% regressed; none of the regressed lesions were accompanied by RPE atrophy. Conclusions: Pachydrusen, defined as late-phase ICGA hyperfluorescence, was predominantly distributed outside the ETDRS grid with a superotemporal predilection and could increase or decrease over a 5-year follow-up period. No colocalization with MNV was observed, and no accompanying RPE atrophy after pachydrusen regression was identified, suggesting that late-phase ICGA–hyperfluorescent pachydrusen may represent a pathophysiology distinct from that of soft drusen. Full article

Background: Age-related macular degeneration (AMD) is the primary cause of severe visual acuity loss in individuals over 60 with increasing prevalence. Currently, no effective treatments exist for geographic atrophy and macular scarring, highlighting the need for visual rehabilitation in these patients. Microperimetry offers functional assessment at any AMD stage and employs fixation training to help patients utilize the most effective retinal areas for vision. Methods: A prospective study involving 25 patients (50 eyes) aged 67 to 90. The MAIA II microperimeter assessed scotoma size and location, retinal sensitivity, macular integrity, fixation parameters (P1, P2, 63%BCEA, 95%BCEA), fixation stability, and preferred retinal locus. Quality of life was evaluated using the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). A subgroup with inactive AMD-related macular changes, either bilateral geographic atrophy (13 patients, 26 eyes) or bilateral scarring (12 patients, 24 eyes), was identified, all exhibiting bilateral absolute central scotomas of at least 2 degrees. Each patient completed 10 fixation training sessions with a microperimeter, training the eye with better acuity weekly. One-week post-training, a functional assessment was performed on both trained and untrained eyes. Results: Fixation training significantly improved best corrected visual acuity (BCVA) in trained eyes (mean change −0.14 logMAR, p < 0.001, large effect size) and also in fellow untrained eyes (−0.16 logMAR, p < 0.001). BNVA improved from 2.25 to 1.86 in trained eyes (p < 0.001) and from 2.96 to 2.76 in untrained eyes (p = 0.004). Fixation stability parameters improved significantly, including increases in P1 and P2 and reductions in Bivariate Contour Ellipse Area (BCEA). Quality of life measured using the NEI-VFQ-25 questionnaire improved significantly in 9 of 11 domains. Conclusions: Microperimetry may be a valuable tool for assessing visual function in AMD patients. Fixation training with the MAIA II microperimeter is both safe and effective for vision rehabilitation in those with geographic atrophy and macular scarring. Full article

Background/Objectives: Inherited retinal diseases (IRDs) represent a genetically heterogeneous group of disorders caused by mutations in over 280 genes with more than 3100 identified variants. While gene-specific replacement therapies have achieved landmark success with voretigene neparvovec (Luxturna) for biallelic RPE65-associated retinal dystrophy, developing individual therapies for each genetic subtype remains impractical. This review examines gene-agnostic therapeutic approaches utilizing neuroprotection and immunomodulation that target common pathophysiological mechanisms shared across multiple IRD genotypes. Methods: We reviewed the literature on neuroprotective and immunomodulatory gene therapy strategies for IRDs, focusing on neurotrophic factors and complement system modulation. Results: Neuroprotective approaches delivering neurotrophic factors—including pigment epithelium-derived factor (PEDF), ciliary neurotrophic factor (CNTF), rod-derived cone viability factor (RdCVF), brain-derived neurotrophic factor (BDNF), fibroblast growth factors (FGFs), glial cell line-derived neurotrophic factor (GDNF), and proinsulin—have demonstrated photoreceptor preservation across multiple preclinical IRD models regardless of the underlying genetic mutation. The recent FDA approval of CNTF cell-based gene therapy (Encelto) for macular telangiectasia type 2 validates this therapeutic paradigm. Complement system inhibition represents another gene-agnostic strategy, with intravitreal complement inhibitors approved for geographic atrophy secondary to age-related macular degeneration and gene therapy approaches targeting C3, C5, or delivering soluble complement regulators under investigation for IRDs. Combination strategies simultaneously addressing multiple pathogenic pathways may offer synergistic benefits. Conclusions: Gene-agnostic approaches targeting neuroprotection and immunomodulation offer a therapeutic paradigm capable of benefiting patients across the spectrum of IRD genotypes, potentially transforming treatment for conditions where mutation-specific therapies remain unavailable. Full article

Age-related macular degeneration (AΜD) remains a leading cause of irreversible vision loss. Ιn neovascular AΜD (nAΜD), frequent intravitreal anti-VΕGF injections create substantial treatment burden, while approved therapies for geographic atrophy (GA) provide modest slowing of progression. Ocular gene therapy aims to achieve sustained intraocular expression of therapeutic proteins after a single administration. Τhis review summarises the biological rationale, vector platforms, and delivery routes relevant to AΜD, with emphasis on adeno-associated virus (AAV) systems, capsid engineering, and compartment-specific administration (intravitreal, subretinal, and suprachoroidal). We synthesise the clinical landscape for sustained anti-VΕGF expression approaches in nAΜD and complement-modulating strategies for GA, and highlight how trials increasingly prioritise injection-burden reduction, anatomical endpoints, and biomarkers of target engagement. Κey challenges include intraocular inflammation and neutralising antibodies (particularly with intravitreal dosing), variability and durability of transgene expression, surgical risks associated with subretinal delivery, and practical constraints related to manufacturing scale, cost, and long-term safety surveillance for non-removable therapies. Overall, gene therapy offers a plausible route towards durable, mechanism-targeted AΜD management, but its clinical role will depend on robust controlled trials and multi-year follow-up. Full article

Pathologic myopia has become a major global cause of blindness, making timely surgical management for myopic traction maculopathy (MTM) increasingly important. This study aimed to identify prognostic factors associated with functional and anatomical outcomes following surgery for MTM and to determine the optimal timing for intervention. This retrospective study included 33 eyes from 28 patients with MTM without full-thickness macular hole who underwent pars plana vitrectomy with internal limiting membrane peeling and gas tamponade. Better preoperative best-corrected visual acuity (BCVA) and lower foveal height were associated with better postoperative BCVA, whereas longer axial length, higher MTM, and higher Atrophy–Traction–Neovascularization (ATN) classification grade were correlated with thinner postoperative central foveal thickness. Foveal detachment (FD), ellipsoid zone (EZ) disruption, and advanced MTM grade were associated with poorer functional and anatomical outcomes. Postoperative visual outcomes should be interpreted with caution, as they may have been influenced by lens-related factors, including combined cataract surgery, post-vitrectomy cataract progression, and posterior capsule opacity. Nonetheless, consistent anatomical improvement was observed, supporting early surgical consideration in eyes with MTM showing progressive macular traction or EZ disruption, even in the absence of FD. These findings highlight the importance of serial OCT monitoring and individualized surgical timing based on preoperative assessments. Full article

Background: Inflammatory hyperreflective retinal foci (I-HRF) have been recognized as an optical coherence tomography (OCT) biomarker of aggregates of activated microglial cells. Microglia, the principal resident immune cells, are key players in geographic atrophy (GA) development and progression. Objective: To quantify I-HRF distribution across inner (IR) and outer (OR) retinal layers in GA compared with healthy controls. Methods: Retrospective observational study including patients aged ≥50 years with GA lesion area >1.25 mm² and age-matched healthy subjects. GA eyes were classified as bilateral GA (B-GA) or unilateral GA (U-GA; fellow eye with macular neovascularization). Using Spectralis OCT, I-HRF (≤30 μm; RNFL-like reflectivity; no posterior shadowing) were identified and counted across IR and OR. Results: Sixty-eight eyes from 46 patients with GA (B-GA: 49 eyes; U-GA: 19 eyes) and 19 control eyes were studied. I-HRF were higher in IR than in OR in all groups (p < 0.001). I-HRF were higher in GA eyes in both layers compared with controls (p < 0.05). U-GA exhibited higher I-HRF than B-GA in IR (44.32 ± 8.47 vs. 30.10 ± 7.62; p < 0.001), while I-HRF were not significantly different in OR (9.58 ± 3.04 vs. 8.02 ± 3.33; p = 0.081). Conclusions: I-HRF are increased in GA. They are more numerous in IR, consistent with their proposed inflammatory origin. These findings further support the role microglia may play in GA pathology. I-HRF may become an OCT biomarker to track GA-associated neuroinflammation in different GA phenotypes. Longitudinal studies are needed to clarify I-HRF significance in GA progression. Full article

Age-related macular degeneration (AMD) is the leading cause of central vision loss in aging populations. Geographic atrophy (GA) is the advanced, non-neovascular form of AMD. Predicting the longitudinal progression of GA remains a critical challenge in ophthalmic clinical practice and clinical trial design. Forecasting the trajectory of GA is complicated by highly variable growth rates and the inherent scarcity of long-term, high-quality imaging data. To address these challenges, we introduce the Sliding Window Attention U-Net (SWAU-Net), a hybrid architecture that integrates Transformer-based temporal modeling of GA growth with precise spatial modeling of GA location with a U-Net convolutional neural network (CNN). To ensure generalization in the low-data regime, SWAU-Net embeds explicit temporal and geometric consistency priors via a weight-shared Sliding Window Attention core and feature-level regularization that preserves sparse, high-frequency lesion boundaries across frames. Experimental results demonstrate that these structural constraints prevent the model from overfitting to imaging noise, achieving a Growth Mask Dice Similarity Coefficient (DSC) of 0.66 (representing the spatial overlap between the predicted and ground truth lesion expansion regions), a significant improvement over unregularized Transformer and standard recurrent baseline models. Our framework provides a robust tool for predicting GA lesion trajectories, potentially supporting more efficient clinical trial designs and personalized patient monitoring. Full article

Background: The implantable miniature telescope is used to provide functional vision for patients with advanced AMD. However, despite the considerable cost of the device, there are strict criteria to be met for this procedure, since the patients require challenging neuroadaptation afterward, which sometimes fails and leads to the necessity of device explantation. Visual outcomes also depend on the stability of the microtelescope; tilts cause unwanted optical aberrations and can lead to device luxation, with sight-threatening complications. Case report: This case presents a novel technique for fixing the ophthalmic telescope device SING-IMT™. A 76-year-old female with pre-operative visual acuity of 15 letters on the ETDRS scale underwent surgery on her left eye. The superior haptic was fixed at the 12 o’clock position with a Prolene 5-0 suture, achieving good postoperative stability. The implant was stable throughout the entire observation period. Conclusions: Implant stability is crucial for maximizing visual potential in patients with advanced AMD selected for the procedure, since visual acuity in the peripheral retina, where the perceived image eventually lands, is much lower than the macula. Therefore, there is a need to standardize surgical approaches and use objective follow-up measures to assess long-term patient satisfaction. Full article

Age-related macular degeneration (AMD) is an increasingly prevalent source of permanent visual impairment in the aging population and is widely accepted as a multi-factorial neurodegenerative disorder of the retina. While there has been significant progress in treating neovascular AMD, there are currently no effective disease-sparing treatments for dry AMD and geographic atrophy. To date, research has begun to reveal the complex relationship between the environment and genetic predisposition in AMD pathogenesis. Various environmental factors responsible for AMD include oxidative stress, mitochondrial dysfunction, inflammation, abnormal complement activation, and epigenetic regulation, which interact dynamically to drive disease progression. This review summarizes recent data and provides a comprehensive model for understanding how these interacting factors lead to the progression of AMD from an early stage to advanced stages with complications associated with the disease. We highlight the central role of retinal pigment epithelial mitochondrial failure and impaired stress resilience as upstream drivers that amplify inflammation and complement-mediated injuries. We also discuss how dysregulated miRNAs and proteomic network remodeling contribute to disease heterogeneity. Emerging therapeutic strategies are reviewed in the context of molecular endotyping and personalized intervention. Finally, we outline future directions toward precision medicine in AMD, emphasizing early disease modification, rational combination therapies, and the need to bridge the translational gaps between molecular discovery and clinical trial design. Full article

Varicella-Zoster Virus (VZV) is one of the most important pathogens in ophthalmology. Reactivation may involve the adnexa (blepharoconjunctivitis, pseudomembranous conjunctivitis), cornea (dendritic keratitis, nummular and necrotizing stromal keratitis, disciform endotheliitis, neurotrophic ulcers, mucous-plaque keratitis) and sclera (episcleritis, anterior scleritis). Uveal inflammation ranges from anterior uveitis—with iris atrophy, trabeculitis-induced glaucoma and complicated cataract—to posterior necrotizing syndromes: acute retinal necrosis in immunocompetent hosts and progressive outer retinal necrosis in immunosuppressed patients, often complicated by occlusive vasculitis, macular edema, retinal detachment and phthisis. Optic nerve and cranial nerve involvement (optic neuritis, neuroretinitis, III/IV/VI palsies) and orbital inflammation may occur even without cutaneous signs (“zoster sine herpete”), making PCR-based intraocular diagnostics essential. Management relies on early, high-dose antivirals (acyclovir or valacyclovir), judicious corticosteroids and timely surgical intervention when required. Universal childhood varicella vaccination and recombinant zoster vaccination in adults ≥50 years have reduced VZV incidence and ocular complications in settings with high vaccine coverage, though rare post-vaccine keratitis or uveitis underscore the need for ongoing vigilance. In this review, we synthesize current knowledge on varicella-zoster virus ocular disease, with a focus on host–pathogen interactions that drive both injury and defense. Full article

Background/Objectives: Clinical differentiation between Parkinson’s disease (PD) and atypical parkinsonism (AP) remains complex. Current diagnostic procedures helpful in their distinction lack specificity, making non-invasive tools like optical coherence tomography (OCT) crucial in evaluating possible retinal changes as potential biomarkers. Our study examined the thickness of the ganglion cell inner plexiform layer complex (GCIPL), peripapillary retinal nerve fiber layer (RNFL) and macular segments in individuals with PD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and healthy controls (HC). The objective of our study was to determine if OCT analyses can effectively discriminate PD patients from HC and whether retinal thickness can distinguish typical PD patients from those with AP. Methods: Research was an observational, cross-sectional study. Multiple retinal layers measured with OCT of PD and AP patients were compared with age- and sex-matched HC. An intergroup assessment was conducted. Results: Patients with PD and PSP exhibit a thinner GCIPL compared to HC, with no difference observed in the MSA group. GCIPL thickness between investigational groups does not differentiate between PD and AP. The RNFL and central macula thickness were statistically significantly reduced in all patient groups compared to HC. The RNFL was thinner in PSP compared to PD. Nearly all inner and outer macular segments were thinner in the investigational groups compared to HC. The preservation of outer nasal segments distinguished HC from both typical and AP. Patients with PSP and PD differed in the thickness of all macular segments, being thinner in PSP patients. Conclusions: Thickness of multiple retinal layers and macular regions might serve as a distinguishing feature between PD, AP and HC. Full article

Geographic atrophy (GA) is a progressive cause of central vision loss with limited rehabilitation options. This prospective case series aimed to evaluate the effects of biofeedback fixation training (BFT) on visual function and vision-related quality of life (QoL) in patients with GA. Eighteen patients with total central vision loss in one eye underwent BFT on the fellow eye (study eye) using the Macular Integrity Assessment (MAIA) system, which was used to select a new, previously chosen preferred retinal locus (PRL) to stabilize fixation or adopt a new fixation locus. Patients were followed for an average of 13.2 months (range 3–26 months). Functional outcomes included best corrected visual acuity (ETDRS chart), reading performance (Radner test), and contrast sensitivity (Spot Checks test). MAIA parameters comprised average retinal sensitivity, fixation distance and stability (P1, P2), and changes in the bivariate contour ellipse area (BCEA). Vision-related quality of life was assessed using the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25). Following BFT, visual acuity, reading ability and contrast sensitivity improved significantly (p value: p < 0.02), and fixation stability and NEI-VFQ-25 scores showed a positive trend. These findings indicate that BFT is a feasible and promising rehabilitation approach for patients with GA. Full article

Aim: To report on the clinical and genetic spectrum of retinopathy associated with CDHR1 variants in a Hungarian cohort. Methods: A retrospective cohort study was conducted at a single tertiary care referral center. The study enrolled nine patients harboring biallelic variants in the CDHR1 gene. Detailed clinical history, multimodal imaging, electroretinography, and molecular genetics are presented. Results: We identified four CDHR1 variants predicted to cause loss-of-function and five phenotypes (cone dystrophy, central areolar choroidal dystrophy, cone-rod dystrophy, rod-cone dystrophy, and late-onset macular dystrophy). The most frequent variant was the synonymous CDHR1 c.783G>A (p.Pro261=) variant (10/18 alleles, 55.6%). A novel splice acceptor site variant, CDHR1 c.349-1G>A, and a novel intronic variant, CDHR1 c.1168-10A>G, were also detected. Fundus examination revealed macular atrophy with or without peripheral retinal changes. Full-field electroretinography, available in seven patients, demonstrated decreased light-adapted and extinguished dark-adapted responses in both the rod-cone dystrophy group and patients with macular involvement. OCT imaging indicated ellipsoid zone disruption with foveal sparing in two out of nine patients and severe retinal damage in rod-cone dystrophy cases. Conclusions: The predominant clinical manifestations of cone dystrophy, cone-rod dystrophy, and macular dystrophy in the Hungarian patient cohort showed heterogeneity, with a rod-cone dystrophy phenotype observed in five of nine cases (55.6%). The natural history of CDHR1-associated retinopathy typically follows a slow progression, providing a therapeutic window, which makes the disease a candidate for gene therapy. Full article

Background/Objectives: The influence of the vitreoretinal interface on neovascular age-related macular degeneration (nAMD) remains poorly characterized. Most previous studies relied solely on macular optical coherence tomography (OCT), which provides limited information about global posterior vitreous detachment (PVD). This study evaluated (1) whether ultrasonography-defined PVD status differs between nAMD eyes and healthy controls, and (2) whether baseline PVD influences macular neovascularization (MNV) phenotype and functional outcomes following anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: In this prospective longitudinal study, treatment-naïve nAMD eyes and population-based healthy controls underwent dynamic B-scan ultrasonography and spectral-domain OCT. PVD was categorized as absent, partial, or complete. nAMD eyes received intravitreal aflibercept according to a treat-and-extend protocol and were followed for 12 months. Structural parameters—including subretinal fluid (SRF), intraretinal fluid (IRF), and central foveal thickness—along with best-corrected visual acuity (BCVA) were recorded. A multivariable linear regression model was performed to assess whether PVD independently predicted BCVA gain after adjusting for age, baseline BCVA, MNV subtype, SRF, atrophy, and number of injections. Results: Absence of PVD was significantly more frequent in nAMD eyes than in controls (p < 0.001), whereas complete PVD prevalence was comparable. In nAMD, absence of PVD was associated with a higher prevalence of MNV type 2 (p = 0.032), while partial/complete PVD correlated with type 1 lesions. After 12 months, eyes without PVD achieved the greatest visual improvement (mean BCVA gain +0.34 ± 0.26), outperforming eyes with complete PVD (p = 0.026). A multivariable model confirmed that absence of PVD was an independent predictor of greater BCVA gain (β = −0.27; 95% CI −0.42 to −0.12; p = 0.0008). Eyes with complete PVD required more injections (p = 0.046). SRF and foveal-thickness reductions occurred across groups, whereas IRF changes were similar. Conclusions: Ultrasonography-defined PVD status differs markedly between nAMD and healthy eyes and independently influences neovascular phenotype and functional response to anti-VEGF therapy. These findings underscore the physiological importance of the vitreoretinal interface and support the use of ocular ultrasonography as an adjunct tool for assessing global vitreous status in selected nAMD settings. Full article