Across Europe, children living with low vision often face inconsistent approaches to the assessment of their visual function, leading to delays in diagnosis and unequal access to care. To address this gap, a multidisciplinary group of experts from eight European countries developed a clinical consensus statement (CCS), using a modified Delphi process. This CCS provides guidance on evaluation of primary visual functions in children with low vision, regardless of etiologies. Testing visual function can be challenging, and cannot be limited to testing visual acuity. It requires a comprehensive approach that takes into account the child's developmental age and necessary adjustments for vision loss. This consensus presents different validated tools to evaluate visual acuity, contrast sensitivity, visual field, and color vision. It provides practical guidance for their use across developmental stages, including infancy and in children with syndromic or neurodevelopmental conditions, and highlights the critical role of caregivers in ensuring reliable assessments. The recommendations emphasize the need for age-appropriate testing strategies, tailored adaptations for low vision and additional impairment, and the importance of early assessment to support timely habilitation and optimize developmental outcomes.
Iridocorneal endothelial (ICE) syndrome is a rare acquired anterior segment disorder characterized by abnormal proliferation and migration of corneal endothelial cells, leading to progressive angle closure, iris abnormalities, secondary glaucoma, and corneal decompensation. Historically divided into Chandler syndrome, progressive iris atrophy, and Cogan-Reese syndrome, ICE is now recognized as a disease spectrum with a shared pathophysiologic basis. Diagnosis and management remain challenging because of variable clinical manifestations and progressive vision-threatening complications. We provide a comprehensive review of ICE syndrome, presenting an updated overview relevant to ophthalmologists on epidemiology, pathogenesis, multimodal diagnosis, differential diagnosis, and current management strategies while highlighting emerging molecular insights and future therapeutic directions.
Subretinal surgery has evolved from a niche indication for choroidal neovascular membrane excision to a versatile microsurgical platform enabling gene and cell therapy delivery, submacular hemorrhage displacement, and removal of subretinal fibrosis or proliferative vitreoretinopathy membranes. Across these indications, the creation of a controlled subretinal bleb and atraumatic manipulation of the neurosensory retina are the technical cornerstones. Recent advances - including intraoperative optical coherence tomography, high-gauge instruments, and robotic assistance - have markedly improved surgical precision and safety. We summarize current subretinal surgical applications, describing the principles, techniques, and clinical evidence underlying each, as well as common complications and future directions toward standardized, image-guided, and robotic subretinal intervention.
No light perception (NLP) vision is the most severe measurable level of visual loss. Recovery is widely understood to be possible in some settings, but its probability has never been quantified across etiologies. Following PRISMA 2020 and MOOSE guidelines (PROSPERO: CRD420261337887), we searched 4 databases from inception to March 11, 2026. The search captured a broad, prespecified range of ocular etiologies, but only open globe injury (OGI), traumatic optic neuropathy (TON), and autoimmune optic neuritis yielded NLP-specific subgroups large enough to pool. Of 37 included studies, 24 (1339 eyes) entered quantitative synthesis. Pooled recovery to light perception or better was 43.3% (95% CI: 33.8-53.1%), with considerable heterogeneity (I² = 89.8%); recovery was strongly etiology-dependent: autoimmune optic neuritis 92.1%, TON 44.6%, OGI 37.4%. Recovery to ≥ 20/200 occurred in 12.1% of eyes and to ≥ 20/40 in 1.5%. Certainty of evidence was very low. NLP is therefore not a single prognostic entity: the probability of recovery differs roughly 2- to 3-fold by etiology, while recovery of functional acuity remains uncommon irrespective of cause. Prognosis should be framed by mechanism rather than by acuity alone.
Iris lesions encompass a broad spectrum of entities ranging from benign pigmentary variants to primary malignancies and secondary infiltrative or metastatic disease. Although many are discovered incidentally and remain asymptomatic, certain lesions may exhibit growth, seeding, hyphema, pigment dispersion, or angle involvement, leading to secondary glaucoma and vision loss. We synthesize contemporary evidence on melanocytic, non-melanocytic, and cystic iris lesions. We highlight a multimodal diagnostic approach incorporating slit-lamp biomicroscopy with serial photography, gonioscopy, iris transillumination, anterior segment optical coherence tomography, and high-frequency ultrasound biomicroscopy to characterize lesion architecture and define posterior extension. Ancillary testing, including dilated fundus examination and cross-sectional imaging, is discussed when ciliary body involvement or extra-iris disease is suspected. Management strategies are summarized, including surveillance thresholds, indications for biopsy, and treatment options for malignant or symptomatic lesions, with particular attention to prevention and control of secondary glaucoma.
Optic disc melanocytoma (ODM) is a benign pigmented tumor historically regarded as stationary. ODM can produce visual dysfunction and rarely undergoes malignant transformation. We synthesize evidence on predicting visual field defects and recognizing malignant transformation. Optical coherence tomography angiography (OCTA) studies demonstrate that visual field defects correlate more strongly with absent intratumoral blood vessel networks than with tumor size. A validated threshold of capillary density loss > 0.75% per year identifies patients at increased risk of visual field progression. OCTA measurements demonstrate high intra-device reproducibility (intraclass correlation coefficients >0.8) but poor inter-device reliability, requiring strict standardization. Regarding malignant transformation, a synthesis of case series indicates a rate of approximately 1.7%, with transformation potentially occurring decades after diagnosis. OCTA detects malignant transformation through identification of intrinsic tumor vasculature. In choroidal studies, intralesional vessel diameter ≥ 76.3μm has demonstrated 100% sensitivity and specificity for distinguishing melanoma from nevus; however, ODM-specific validation is needed. Key warning signs include progressive tumor growth, unexplained vision loss, vitreous seeding, and intrinsic tumor vasculature. Evidence-based surveillance protocols recommend imaging every 3-6 months for the first 2 years after detection of high-risk features, then annually if stable. These findings support long-term surveillance with multimodal imaging and standardized quantification protocols.
Chronic ocular surface pain (COSP) is a debilitating condition of the eye driven by nociceptive, nociplastic, and neuropathic mechanisms. While individual studies using functional neuroimaging techniques to investigate ocular pain exist, the full extent, methodologies, and cumulative findings of this body of literature have not been systematically synthesized. Using a systematic review approach, we identified 5 articles evaluating the use of functional neuroimaging in COSP patients from an initial pool of 643 unique studies. All studies used functional magnetic resonance imaging exclusively as their functional neuroimaging modality, and 4 included photophobia as a manifestation of COSP. Across the studies, there were a total of 107 adult patients enrolled, of whom 83 were cases (37.3% female) with active COSP/photophobia and 24 were controls (29.2% female). The results of the studies demonstrate that light robustly recruits trigeminocortical nociceptive networks (spinal trigeminal/brainstem, S1, insula, anterior midcingulate), with partial attenuation after interventions such as topical anesthesia, botulinum toxin, or FL-41 lenses. Mechanistically, photophobia may reflect convergence of melanopsin/intrinsically photosensitive retinal ganglion cells signaling with trigeminothalamic pathways, motivating brain-based biomarkers alongside surface metrics. The consistency in study design, imaging hardware, and analytical pipelines across the 5 primary articles facilitates direct comparison but also highlights current limitations in the broader generalizability and diversity of the field. Notably, the paucity of neurophysiological studies limits our mechanistic understanding of COSP in terms of neural oscillations that can be potential targets of neuromodulatory interventions.
Macular atrophy (MA) is a major cause of long-term visual decline in neovascular age-related macular degeneration (nAMD), despite the ability of anti-vascular endothelial growth factor (anti-VEGF) therapy to control exudation. We summarize current evidence on the definition, epidemiology, risk factors, imaging features, and functional consequences of MA in nAMD. Optical coherence tomography (OCT) has improved the identification of atrophic changes and supports distinguishing complete retinal pigment epithelium (RPE) and outer retinal atrophy from fibro-atrophy, a proposed OCT-based category in which outer retinal and RPE loss occur beneath hyperreflective or fibrotic tissue that makes choroidal hypertransmission absent or unassessable. In treated eyes, long-term studies show that MA becomes increasingly common over time and is a major factor limiting durable visual benefit, yet epidemiologic estimates remain difficult to compare because MA definitions, imaging modalities, lesion-size thresholds, and terminology varies substantially across studies. Important risk factors include older age, poor baseline visual acuity, type 3 macular neovascularization, intraretinal fluid, subretinal hyperreflective material, and early atrophic signs on baseline imaging, whereas type 1 neovascularization may be associated with slower atrophy progression. Once established, MA substantially affects visual function, not only reducing visual acuity, but also impairing reading speed and other visual functions. A major unresolved controversy is whether cumulative anti-VEGF exposure contributes independently to MA, rather than reflecting more severe or recurrent exudative disease. Future progress will depend on standardized definitions, multimodal imaging, and predictive models to guide personalized management and develop therapies targeting atrophy.
Preloaded Descemet membrane endothelial keratoplasty (plDMEK), in which eye-bank validated donor tissues are prepared, folded, and loaded into delivery devices prior to shipment, has emerged as a promising strategy to standardize and expand access to endothelial keratoplasty. Protocols developed with both endothelium-in (endo-in) and endothelium-out (endo-out) loading configurations have shown to improve surgical efficiency, reproducibility, and tissue utilization while lowering procedural barriers. We compiled current laboratory and clinical evidence on plDMEK and compared endo-in versus endo-out techniques to inform best practices. Following PRISMA guidelines, studies published between June, 2016, and August, 2025, were identified through PubMed, Scopus, Web of Science, and Google Scholar. Thirty-nine studies met inclusion criteria (19 clinical, 20 laboratory). Across 1420 clinical eyes, the overall sample size-weighted rebubbling rate was 25.5%; with rates of 30.4% for endo-in and 19.3% for endo-out grafts. Both configurations produced meaningful visual improvement from baseline (0.18 logMAR for endo-in, 0.12 logMAR for endo-out; p = 0.31) with endothelial cell loss (ECL) of 38% (endo-in) and 32% (endo-out) (p = 0.33) at 12 months. Laboratory studies showed a pooled ECL of 10.2% (9.4% endo-in, 11% endo-out; p = 0.4112) after storing in the delivery device for up to five days. Both approaches appear to be reliable, safe, and clinically acceptable methods for graft preparation and delivery. While endo-out technique shows a trend toward lower post operative rebubbling compared to endo-in, study heterogeneity underscores the need for standardized reporting, longer follow-up, and direct comparative trials to guide global clinical adoption.
Central serous chorioretinopathy (CSCR) has traditionally been regarded as a self-limiting disorder and classified using duration- or phenotype-based frameworks. Accumulating clinical and imaging evidence, however, suggests that CSCR is a recurrent disorder in which choroidal haemodynamic abnormalities and retinal pigment epithelium (RPE) dysfunction interact to determine long-term structural and functional outcomes. We synthesize current advances in choroidal physiology and multimodal imaging to propose the Tap-Drain model, a physiology-based conceptual framework that reconceptualizes CSCR as a disorder of outer retinal fluid homeostasis. Within this framework, fluid entry ("tap") is proposed to arise predominantly from choroidal haemodynamic abnormalities, including vascular hyperpermeability and impaired venous drainage, whereas disease expression may also be influenced by regional variability in RPE functional reserve. Fluid clearance ("drain") is mediated by the RPE, and impaired RPE function may reduce its capacity to compensate for increased choroidal inflow, resulting in persistent or recurrent subretinal fluid (SRF). We further propose a mechanistic staging system and a Corrective Action-Preventive Action (CAPA) framework that aligns management with the predominant imbalance between fluid entry and clearance. By distinguishing tap-dominant, drain-stressed, and drain-failure phenotypes, the framework shifts treatment goals beyond episodic SRF resolution toward recurrence prevention, preservation of retinal structure, and maintenance of long-term visual function. Although biologically plausible and clinically intuitive, the Tap-Drain model remains a conceptual framework that requires prospective clinical validation before its prognostic and therapeutic implications can be considered established.
We evaluat the efficacy and safety of adeno-associated virus-mediated gene therapy for CNGA3- and CNGB3-associated achromatopsia. Human studies were systematically searched from database inception to March, 2026, and 9 studies were included. Pooled analysis showed modest, but statistically significant, improvement in best-corrected visual acuity, with a mean difference of 2.65 ETDRS letters, and significant improvement in contrast sensitivity. Retinal sensitivity did not improve significantly, whereas color discrimination showed small but significant improvement. Dose-stratified findings suggested a non-linear response, with greater benefit at lower to intermediate doses than at the highest dose. Safety analysis indicated an approximate adverse-event probability of 29%, with events generally mild, transient, and manageable. Current evidence suggests favorable short- to mid-term safety and modest functional benefit, mainly in CNGA3-associated achromatopsia, while efficacy in CNGB3-associated disease remains uncertain.
Vision symptoms are frequent after concussion and can often persist and be disabling. Most studies on concussion with persisting concussion symptoms (PCS) provide limited attention to vision symptoms. Vision symptoms occur in 69-82% of patients with PCS and commonly include photophobia, blurred vision, and computer screen intolerance (CSI) - a syndrome induced by viewing electronic screens including computer, cell phone, tablet, or TV screens. We discuss the vision symptoms that may arise and persist after a concussion. Unfortunately, the pathophysiology of many of these symptoms is unknown, and we examine current views of the mechanisms potentially involved with a focus on CSI. We also evaluate the effectiveness of the currently available treatments. Our aim is to improve recognition and treatment of concussion induced vision symptoms through an understanding of their pathophysiology and the efficacy of available treatments. Enhanced recognition and understanding may facilitate improved treatment for these debilitating symptoms that compromise the quality of life and hinder return to school or work for many concussed individuals. We aim to aid ophthalmologists, optometrists, and other vision scientists who are frequently called upon to diagnose and treat patients with these symptoms.
Hard exudates are common fundus findings in retinal vascular disease, but are frequently regarded as passive remnants of vascular leakage rather than biologically meaningful lesions. Traditionally described as lipid deposits associated with diabetic retinopathy and retinal vein occlusion, they have received limited integrative analysis across disease contexts. Emerging insights from vascular biology, lipid metabolism, and multimodal imaging challenge this view and reveal that hard exudates represent organized extracellular lipid-protein aggregates arising from sustained vascular-metabolic dysfunction. We synthesize current evidence on the biochemical composition, pathophysiology, and biophysical behavior of hard exudates, integrating contributions from both retinal and choroidal vascular compartments and dysfunction of the inner and outer blood-retinal barriers. Advances in optical coherence tomography enable precise layer-specific localization, facilitate differentiation from phenotypic mimickers, and support a mechanism-based diagnostic framework. Therapeutic considerations emphasize vascular stabilization over lesion-directed treatment, recognizing delayed and incomplete regression. Finally, emerging quantitative imaging and artificial intelligence-based approaches are discussed as future strategies to reposition hard exudates as dynamic biomarkers of disease chronicity and prognostic risk.
Retinal and choroidal structural alterations have increasingly been recognized in individuals with human immunodeficiency virus (HIV) infection, although findings from optical coherence tomography (OCT) studies remain inconsistent. We evaluated retinal and choroidal thickness changes measured by OCT in HIV-infected individuals compared with healthy controls. A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and Embase from database inception to April, 2025. Studies reporting OCT-based measurements of retinal layer or choroidal thickness (CT) in HIV-infected individuals and healthy controls were included. Standardized mean differences (SMD) were pooled using fixed- or random-effects models. 21 studies involving HIV-infected individuals and healthy controls were included. HIV infection was associated with significant thinning of the macular ganglion cell-inner plexiform layer (SMD -0.55; 95% CI -0.80 to -0.29;P < 0.001), foveal inner plexiform layer (SMD -0.36; 95% CI -0.62 to -0.10;P = 0.006), temporal peripapillary retinal nerve fiber layer (pRNFL) (SMD -0.21; 95% CI -0.40 to -0.02; P = 0.03), and global pRNFL (SMD -0.20; 95% CI -0.38 to -0.02; P = 0.03). Peripheral macular ganglion cell layer (SMD 0.17; 95% CI 0.01-0.32;P = 0.034) and outer plexiform layer thickness (SMD 0.35; 95% CI 0.18-0.52;P < 0.001) were significantly increased. CT was comparable between HIV-infected individuals and healthy controls (SMD 0.15; 95% CI -0.28-0.58;P = 0.49). Overall, HIV infection appears to be associated with selective, layer-specific retinal structural alterations, predominantly affecting inner retinal layers, while CT remains largely preserved. These findings support the concept of HIV-related neuroretinal involvement and suggest that OCT-derived retinal parameters may serve as noninvasive biomarkers for detecting neurodegenerative changes in individuals with HIV infection.
We performed comprehensive systematic review of orbital and periorbital non-familial amyloidosis, including clinical features, radiology, histopathology, management and outcomes. We included English-language articles describing biopsy-proven orbital and periorbital amyloidosis published from inception to February, 2025. Cases without ocular histopathology and familial amyloidosis were excluded. We included 120 studies detailing 168 cases. Most were primary localized amyloidosis. The clinical presentation was variable, resulting in diagnostic uncertainty. Amyloidosis most commonly affects superficial structures, such as the eyelid and conjunctiva. Amyloidosis also affects orbital structures, including extraocular muscles, lacrimal gland, and orbital nerves. Computed tomography typically shows enlargement of the affected structures, sometimes with calcifications. On magnetic resonance imaging, amyloidosis appears iso- to hypo-intense on T1-weighted images and hypointense with heterogeneous signal on T2-weighted sequences, often presenting as an infiltrative or mass-like lesion. Amyloid plaques characteristically demonstrate apple-green birefringence on Congo-red staining. Following diagnosis, systemic evaluation helps identify potential severe complications of disease, including visceral damage, dysfunction, and malignancies. Early diagnosis, consideration of surgical or radiotherapy, and close monitoring are important in preventing disease progression and minimising symptoms. Orbital and periorbital amyloidosis is an important differential for non-specific eyelid mass, conjunctival haemorrhage, or periorbital ecchymosis. Careful evaluation is necessary, especially to identify features of systemic disease.
Non-exudative retinal fluid in age-related macular degeneration (AMD) challenges the long-standing paradigm that any fluid on structural optical coherence tomography necessarily reflects neovascular exudation. Advances in multimodal imaging have revealed that both intraretinal fluid and subretinal fluid (SRF) may arise from non-neovascular mechanisms across intermediate AMD and geographic atrophy (GA). Non-exudative IRF encompasses 3 distinct processes: (1) degenerative mechanisms occurring in progressive atrophy, (2) "burnt-out" contraction with cavitation overlying chronic fibrotic scars, and (3) mechanical stress induced by underlying lesions (e.g., drusenoid pigment epithelium detachment [PED]), subretinal hyperreflective material) or traction at the vitreomacular interface. Non-exudative SRF reflects retinal pigment epithelium pump failure over drusen or drusenoid PEDs, but may also result from alterations within the photoreceptor outer segments (subretinal pseudocysts). Integrating these mechanisms into clinical interpretation shifts management from a fluid-based to a pathophysiology-based approach, recognizing that non-exudative fluid does not respond to anti-vascular endothelial growth factor therapy and instead signals advanced tissue stress and increased risk of GA progression.
Subretinal hyperreflective material (SHRM) is now recognized as a biomarker in neovascular age-related macular degeneration (nAMD), with potential prognostic value for visual and structural outcomes. We synthesize and critically evaluate the evidence on the prognostic role of SHRM characteristics in patients with nAMD. We conducted a systematic search of PubMed, Scopus and Web of Science for studies published between March, 2015, and March, 2025. Eligible studies included human participants with nAMD, under anti-vascular endothelial growth factor (anti-VEGF) treatment, in which SHRM was assessed using optical coherence tomography and outcomes included best-corrected visual acuity (BCVA), fibrosis and macular atrophy. Thirty-three studies met the inclusion criteria. Most of the studies demonstrated a significant association between the presence of SHRM and worse BCVA over time, particularly correlated to SHRM thickness, width or persistence after anti-VEGF therapy. Well-defined and hyperreflective SHRM was repeatedly linked to poorer functional outcomes. Twelve studies reported SHRM as a strong predictor of subretinal fibrosis, with larger size, defined borders and persistence conferring the greatest risk. The relationship with macular atrophy was less clear; while some studies suggested that thicker or persistent SHRM increased the likelihood of atrophy, others found no association. Overall, the evidence suggests that SHRM is a strong imaging biomarker of poor prognosis in nAMD. While this review highlights consistent patterns, differences in how SHRM is measured remain a limitation. It will be important for future research to standardize SHRM assessment and establish its use in personalized treatment decisions.
