ABSTRACT Background KCNV2‐associated retinopathy is a rare inherited retinal dystrophy caused by variants in the KCNV2 gene, leading to disrupted photoreceptor behaviour and progressive deterioration of vision. Patients have characteristic electroretinography abnormalities, including reduced cone response, delayed and reduced rod response to low light flashes and paradoxically large rod‐driven response to bright flashes of light. To model this condition, we have generated a Kcnv2 E151X mouse line and assessed its structural and functional retinal features. Methods We have employed CRISPR/Cas 9 gene editing technology to generate a mouse line with an early stop mutation in position E151—orthologous to the commonly encountered E143X mutation in humans—and performed a combination of immunohistochemistry and Western blot to confirm the absence of the full‐length KCNV2—encoded protein, Kv8.2. Next, to assess how closely it models the human disease, we have characterised the KCNV2 mutant mouse line at histological and functional levels, via immunohistochemistry and electroretinography experiments, respectively. Results Kcnv2 mutant mice showed markedly reduced photopic responses and reproduced the supernormal rod phenotype described in affected individuals. In the morphological context, mutant retinas demonstrated strong glial fibrillary acidic protein upregulation together with reduced cone arrestin positive cell counts and photoreceptor layers, indicating photoreceptor loss. Conclusions The Kcnv2 mutant mouse line replicates key functional and structural hallmarks of KCNV2‐associated retinopathy. This model provides a relevant platform for mechanistic studies and preclinical evaluation of gene‐based or pharmacological therapies targeting cone and rod photoreceptor dysfunction.
BACKGROUND:To determine whether axial length-related magnification correction in optical coherence tomography angiography (OCTA) improves machine learning classification of high myopia and resolves inconsistencies in the values and discriminatory power of OCTA microvascular metrics. METHODS:We analysed retinal OCTA images from a prior Hong Kong Polytechnic University study. Fourteen superficial vascular plexus metrics were extracted before and after magnification correction and used to train random forest (RF) models to classify high versus non-high myopia. Outcomes included classifier performance (the area under the receiver operating characteristic curve (AUC), sensitivity, specificity and feature importance) and changes in OCTA metrics between groups before and after correction. RESULTS:Image magnification correction significantly improved the classification of high versus non-high myopia. When all 14 features were used to train the model, the AUC increased from 0.77 (fair) to 0.88 (good), and when restricted to the top five features (fractal dimension (Df), vessel length density (VLD), branchpoint density (BD), parafoveal rim VLD, and vessel area density (VAD)), similarly, from 0.79 to 0.88. CONCLUSIONS:OCTA image magnification correction improves RF classification of high myopia and clarifies inconsistencies across studies. Underreported metrics, fractal dimension, parafoveal rim VLD and BD, emerged as key discriminators. Magnification correction with ML may improve characterisation of myopia-related microvascular changes and enhance diagnostic precision, warranting further study.
BACKGROUND:This trial aimed to evaluate the efficacy of oral acetazolamide in reducing cystoid fluid collections (CFC) and improving visual function in patients with X-linked retinoschisis (XLRS). METHODS:In this investigator-initiated, single centre, open-label, randomised controlled trial, XLRS patients aged ≥ 12 years with fovea-involving CFC at baseline were eligible. Participants were randomised 1:1 to receive either oral acetazolamide (500 mg/day for 16 weeks, followed by tapering or discontinuation based on response) or no treatment (control) for 32 weeks. Seven study visits were completed over 32 weeks. The primary outcome was central subfield thickness (CST). Secondary outcomes included functional and structural measures, as well as patient-reported visual disability. RESULTS:A total of 19 patients were enrolled: 10 received acetazolamide (17 eyes), and nine were monitored without treatment (16 eyes). The difference in CST from baseline up to week 32 between the treatment and control groups was on average +2.7 μm (p = 0.9; 95% CI, -68.1 to 73.5 μm). Retinal sensitivity on microperimetry showed a modest statistically significant improvement favouring acetazolamide. However, no significant improvements were observed for best-corrected visual acuity, low-luminance visual acuity, cystoid fluid collection volume or patient-reported visual disability in the treatment group compared to the control group. CONCLUSION:This study found no clinically meaningful benefit of oral acetazolamide for reducing CFC or improving visual function in the overall XLRS population. Although structural and functional outcomes were comparable between groups overall, a small subset of patients may experience benefit, suggesting a personalised treatment approach may be warranted.
BACKGROUND:To evaluate the association between the Notch phenomenon and retinal vascular maturation, the time to complete retinal vascularisation, and progression to severe retinopathy of prematurity (ROP) in treatment-naïve infants with early-stage disease. METHODS:In this retrospective observational study, 350 preterm infants with Stage 1-2 ROP managed conservatively were included. The Notch phenomenon was identified based on ICROP-3 criteria. Time to complete retinal vascularisation was assessed using both weeks from birth and postmenstrual age (PMA). Multivariable regression analyses were performed to assess the independent association between the Notch phenomenon and study outcomes after adjustment for gestational age (GA), birth weight (BW), oxygen therapy, and ROP Zone. RESULTS:The Notch phenomenon was identified in 45 infants (12.9%). Among 324 infants with spontaneous regression, Notch(+) infants required significantly longer time to achieve complete retinal vascularisation than Notch(-) infants (14.85 ± 2.62 vs. 11.11 ± 2.45 weeks from birth; p < 0.001). PMA at the time of complete retinal vascularisation was also significantly higher in the Notch (+) group (45.15 ± 2.21 vs. 42.65 ± 1.87 weeks; p < 0.001), a difference confirmed by Kaplan-Meier analysis (median PMA, 45.50 vs. 42.60 weeks; log-rank p < 0.001). Progression to severe ROP occurred more frequently in infants with a Notch (17.8% vs. 5.9%; p = 0.01). After adjustment for GA, BW, oxygen therapy and ROP Zone, the Notch phenomenon remained an independent predictor of progression to severe, treatment-requiring ROP (OR = 5.10, 95% CI 1.95-13.35; p = 0.001). CONCLUSIONS:In treatment-naïve infants with early-stage ROP, the Notch phenomenon is associated with delayed retinal vascular maturation and an increased risk of progression to severe disease, supporting its role as a clinically relevant morphologic risk marker in ROP follow-up.
Glaucoma frequently coexists with cataract, but glaucomatous functional loss, ocular-surface disease, anatomical abnormalities, and treatment-related refractive variability may reduce tolerance of premium intraocular lenses. This narrative review critically appraises evidence relevant to lens selection in glaucoma. Central visual-field status, contrast sensitivity, fixation, disease stability, anterior-segment anatomy, intraocular pressure control, topical treatment, previous or anticipated glaucoma surgery, and lifetime progression risk should inform decision-making. Enhanced monofocal lenses may improve intermediate vision while preserving distance vision and functional reserve in selected patients with ocular hypertension, preperimetric glaucoma, or early, stable open-angle glaucoma. Selected extended depth-of-focus lenses may be considered when central visual function is preserved, whereas toric lenses require regular, repeatable astigmatism and stable capsular-zonular support. Current evidence does not support routine multifocal lens implantation in established glaucoma. Selection should remain individualised, evidence-calibrated and supported by explicit counselling about uncertainty, dysphotopsias, future progression and possible refractive change after glaucoma surgery.
Several benign, inflammatory and malignant lesions can present as iris or anterior chamber masses, including iris naevi, cysts, adenomas, leiomyomas, nodules, vascular tumours, melanomas, metastases, as well as iris and pigment epithelium adenocarcinomas. Fortunately, benign iris lesions are much more common than malignant tumours and many can be diagnosed by clinical and contemporary non-invasive analyses. However, differentiating between enlarging benign and malignant melanocytic lesions remains problematic. Anterior chamber and iris biopsy may include anterior chamber paracentesis and cytology, fine needle aspiration biopsy, vitreous aspiration cutter biopsy, micro-forceps and punch techniques, minimally invasive excision with an anterior chamber device and conventional iridectomy or excision biopsy. However, there may be reluctance from both patient and physician to progress to iris biopsy or excision biopsy as part of a definitive, or staged, management approach for fear of damage to delicate anterior chamber structures, or inadvertent spread of a malignant tumour. This review provides a practical guide to available techniques, highlighting indications, complications and outcomes. Notably, the yield for cytological, histological and cytogenetic results is typically high, significant complications are uncommon, and no cases of external tumour spread have been reported with clear corneal biopsy techniques.
BACKGROUND:To compare the predictive accuracy of ray tracing-based intraocular lens (IOL) power calculation formulas with the Barrett Universal II (BUII) formula in eyes with Fuchs endothelial corneal dystrophy (FECD) undergoing combined cataract surgery and Descemet membrane endothelial keratoplasty (triple DMEK). METHODS:This is a retrospective, single-centre comparative case series. Preoperative biometry was obtained using Scheimpflug tomography (Pentacam AXL) and a swept-source optical coherence tomography-based biometer (IOLMaster 700). IOL power calculations were performed using Barrett Universal II (BUII), Olsen ray-tracing and two OKULIX ray-tracing approaches (paraxial and 2.5-mm pupil). Prediction error (PE) was calculated and trueness, precision, and accuracy were evaluated using robust statistical methods (Eyetemis). A retrospective IOLup1D adjustment was additionally assessed. RESULTS:One hundred forty-nine eyes of 149 patients were enrolled. BUII demonstrated the lowest trimmed mean absolute error (0.74 ± 0.65D) and median absolute error (0.60D), with 72% of eyes within ±1.00D of the target refraction. Olsen ray-tracing showed higher errors (mean absolute error 1.06 ± 1.02D), while both OKULIX approaches performed similarly (0.91-0.92D). Only OKULIX paraxial ray-tracing showed no significant systematic bias (p = 0.450), whereas all other formulas demonstrated a significant hyperopic shift (p < 0.001). After retrospective IOLup1D adjustment, BUII and Olsen achieved comparable accuracy, with Olsen demonstrating the highest trueness. Mean keratometry values measured with the IOLMaster were 0.20 ± 0.63D steeper compared to the Pentacam. CONCLUSION:In triple DMEK eyes, ray tracing-based IOL power calculation did not offer better accuracy compared to BUII. BUII demonstrated the highest accuracy and precision overall. After IOLup1D adjustment, BUII and Olsen achieved comparable accuracy, with Olsen showing the greatest trueness.
Background We aimed to study the trends in microbiology, precipitating causes and outcomes of endophthalmitis in Victoria, Australia, over a 25-year period. To the best of our knowledge, this is the longest study of endophthalmitis in Australia.Methods We conducted a prospective study of all endophthalmitis cases to the Royal Victorian Eye and Ear Hospital, a state-wide tertiary referral centre for ocular conditions, thereby capturing nearly all state-wide endophthalmitis cases. All patients presenting with endophthalmitis were included. Demographic data, examination findings, microbiology, management and outcomes were collected.Results A total of 1423 eyes from 1408 patients were included. The mean (SD) age was 71.35 (16.12). The median presenting best-corrected visual acuity was hand movements. Cataract surgery formed the plurality of annual cases until 2009; intravitreal injections exceeded following. The rate of endophthalmitis secondary to cataract surgery decreased from 0.29%-0.02% over the 25-year period, with a significant decrease following the introduction of prophylactic cefazolin; however, the rate of endophthalmitis secondary to intravitreal injections remained relatively stable (0.01%-0.04%). 63.03% were culture-positive; the plurality grew gram-positive bacteria (42.94%). Visual outcomes were biphasic; 44.99% had a final BCVA of less than 6/60 (including enucleation/evisceration), while 30.6% reached 6/12 or better. Poor visual outcomes were associated with corneal infection; cataract surgery and intravitreal injections were associated with better outcomes.Conclusions This study demonstrated declining rates of endophthalmitis secondary to cataract surgery and stable rates of endophthalmitis secondary to intravitreal injections. Visual outcomes were bimodal; while many do very poorly, some have good visual recovery.
Background The adoption of angle-based minimally invasive glaucoma surgery (MIGS) procedures has accelerated in recent years; however, inherent limitations remain. Imaging-based techniques across the pre-, intra- and post-operative stages of surgery may facilitate patient selection and improve surgical outcomes. This systematic review explores the application of imaging-based techniques to visualise aqueous humour outflow (AHO) in angle-based MIGS.Methods A literature search was performed on PubMed, EMBASE and Cochrane Library from inception to 16 February 2025. Cohort, cross-sectional and observational studies reporting the use of imaging-based techniques to visualise AHO in angle-based MIGS were included in this review.Results An initial 393 studies were identified, with 21 studies included in final analysis. Imaging techniques reported in literature included various methods to directly observe episcleral veins, haemoglobin venous imaging (HVI), fluorescein and indocyanine green (ICG) aqueous angiography, channelogram and anterior segment optical coherence tomography angiography (AS-OCTA). Visualisation of AHO pre- and intra-operatively may predict surgical outcomes, aiding in patient selection and surgical prognostication. Intra-operative imaging may facilitate targeted placement of MIGS in areas of initially angiographically low or high areas of AHO. AHO assessment pre-, intra- and post-operatively may allow comparative analysis of surgical success and efficacy across various angle-based MIGS.Conclusions Imaging-based techniques visualising AHO have significant potential to improve surgical outcomes of angle-based MIGS.
Background Hyperreflective foci identified on optical coherence tomography are promising biomarkers in age-related macular degeneration. However, their clinical application is limited by inconsistent definitions and ongoing uncertainty regarding their cellular origin. This review critically evaluates the evidence underlying hyperreflective foci definitions, examines competing hypotheses of cellular origin, and assesses their clinical utility.Methods A structured critical review was conducted using a systematic search of MEDLINE and Scopus in July 2025, identifying 164 publications reporting hyperreflective foci in age-related macular degeneration. Eligible studies included clinical imaging, clinicopathological, and histological investigations. Given substantial heterogeneity in study design and outcome measures, findings were synthesised interpretively across three domains: imaging definitions, cellular origin, and clinical associations.Results Clinical OCT definitions for hyperreflective foci were heterogeneous across studies. Histologically, hyperreflective foci correspond to pigment-laden epithelioid cells that consistently express monocyte/macrophage markers (CD68, CD163, IBA1) and lack retinal pigment epithelium markers (RPE65, peropsin). These cells are interpreted as pigment-containing macrophages that have ingested RPE-derived material, or as transdifferentiated RPE cells. Clinically, increasing hyperreflective foci burden is associated with disease severity, progression to geographic atrophy, and localised functional deficits, although associations with neovascular conversion and treatment response are inconsistent.Conclusions The available evidence suggests hyperreflective foci are pigment-containing immune cells, although altered or displaced retinal pigment epithelium cells may also be involved, and independent replication is required. Interpreting hyperreflective foci within this biological context may refine their role in disease monitoring and risk stratification. Establishing consensus imaging criteria, grounded in cellular identity, will be important for clinical translation.
BACKGROUND:To evaluate ocular blood flow in school-aged children born prematurely, with or without retinopathy of prematurity (ROP), using laser speckle flowgraphy (LSFG), and to determine factors associated with LSFG-derived parameters. METHODS:This cross-sectional observational study included 123 school-aged preterm children: 54 without ROP, 20 with untreated type 2/mild ROP, and 49 with treated type 1 ROP. All participants underwent ophthalmic examinations and optic nerve head (ONH) perfusion assessments using LSFG. Mean blur rate indices of the entire ONH (MA), vessel area (MV), and tissue area (MT) of the right eye were analysed. Multivariable generalised linear models were used to identify variables associated with LSFG parameters, and Pearson's correlation was used to examine the association between axial length and MT. RESULTS:Children with type 1 ROP had lower MA, MV, and MT than those with type 2/mild ROP, whereas MV was the highest in the type 2/mild ROP group. Type 1 ROP was independently associated with reduced MA and MV in the full cohort. Among children with ROP, anti-vascular endothelial growth factor (VEGF) treatment was associated with lower MA, MV, and MT. Longer axial length correlated with reduced MT in both the full cohort (r = -0.30, p < 0.01) and the ROP subgroup (r = -0.35, p < 0.01). CONCLUSIONS:Type 1 ROP was associated with reduced ocular blood flow in school-aged children born preterm. Among eyes with ROP, a history of anti-VEGF treatment was associated with lower MA, MV, and MT, although this may reflect disease severity.
