Age-related macular degeneration (AMD) is the leading cause of vision loss and visual impairment in people over 50 years of age. In the current therapeutic landscape, intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies have been central to the management of neovascular AMD (also known as wet AMD), whereas treatments for geographic atrophy have lagged behind. Several therapeutic approaches are being developed for geographic atrophy with the goal of either slowing down disease progression or reversing sight loss. Such strategies target the inflammatory pathways, complement cascade, visual cycle or neuroprotective mechanisms to slow down the degeneration. In addition, retinal implants have been tried for vision restoration and stem cell therapies for potentially a dual purpose of slowing down the degeneration and restoring visual function. In particular, therapies focusing on the complement pathway have shown promising results with the FDA approved pegcetacoplan, a complement C3 inhibitor, and avacincaptad pegol, a complement C5 inhibitor. In this review, we discuss the mechanisms of inflammation in AMD and outline the therapeutic landscapes of atrophy AMD. Improved understanding of the various pathway components and their interplay in this complex neuroinflammatory degeneration will guide the development of current and future therapeutic options, such as optogenetic therapy.

Background: Landmark studies reported on faricimab efficacy and safety predominantly in treatment naïve patients, but outcomes following switch from other anti-VEGF therapies are lacking. We evaluated patients switched to faricimab who had previously shown a partial response to other anti-VEGF injections for neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO). Methods: Retrospective study at the Oxford Eye Hospital. Patients switched to faricimab from January to April 2023 with six months follow-up were identified via electronic medical records. Results: A total of 116 patients (151 eyes) were included. In 88 patients with nAMD (107 eyes), mean visual acuity remained stable: 62±17 ETDRS letters at baseline; 62±18 at six months (p > 0.05). Central subfield thickness (CST) reduced from 294 ± 73 μm to 270 ± 53 μm (p < 0.05) at six months. Subretinal or intraretinal fluid was present in 102 eyes (95%) at baseline and 75 eyes (70%) at follow-up (p < 0.05). Pigment epithelial detachment height decreased from 233 ± 134 μm to 188 ± 147 μm (p < 0.05). Mean treatment interval increased by 1.7 weeks (p < 0.05) and was extended in 61 eyes (57%) at six months. In 28 patients with DMO (44 eyes), visual acuity remained stable: 69 ± 15 letters at baseline; 70±15 at six months (p > 0.05). CST reduced from 355 ± 87 μm to 317 ± 82 μm (p < 0.05). Mean treatment interval increased by 1.4 weeks (p < 0.05) and was extended in 21 eyes (46%) by six months. Conclusions: Switching to faricimab in treatment resistant eyes led to improved anatomical response and extended treatment interval in a significant proportion of patients. Ongoing review of real-world data will inform longer-term outcomes of safety and effectiveness.

Purpose: Corneal collagen crosslinking (CXL) is the primary treatment for progressive keratoconus which has a significant impact on vision and quality of life. Our study aimed to compare the efficacy and safety of epithelium-on versus epithelium-off CXL to treat keratoconus. Methods: We searched PubMed, Medline, Embase, Web of Science, and Scopus databases. We included studies that compared standard epithelium-off with epithelium-on CXL. The primary outcome measures were changes in corrected distance visual acuity (CDVA) and maximum keratometry (Kmax), and the secondary outcomes were uncorrected distance visual acuity (UDVA), central corneal thickness (CCT), and adverse events. A meta-analysis was performed on the primary and secondary outcomes based on the weighted mean differences between baseline to 12-month follow-up. Results: The search retrieved 887 publications with 27 included in the systematic review. A total of 1622 eyes (1399 patients; age 25.51 ± 4.02 years) were included in comparisons of epithelium-off to epithelium-on CXL in keratoconus. Epithelium-off CXL treated 800 eyes and epithelium-on CXL for 822 eyes. At 12-month follow-up, CDVA and Kmax showed no significant difference between the epithelium-off and epithelium-on CXL. The secondary outcomes showed that UDVA was better in epithelium-off CXL (− 0.11D, 95% CI − 0.12, − 0.1; p < 0.001) and there was more thinning in CCT in epithelium-off CXL (− 3.23 μm, 95% CI − 4.64, − 1.81; p <0.001). Conclusion: Epithelium-off and epithelium-on CXL were both effective to treat progressive keratoconus. Further research is needed to compare the long-term outcomes and safety of both CXL protocols for adaptation into clinical practice.

Purpose: Keratoconus is a disorder that results in visual loss from increased corneal high-order aberrations and irregular astigmatism and reduces quality of life. The primary treatment for progressive keratoconus is crosslinking (CXL). Recently, it has been suggested that oxygen enhances the type II photodynamic reaction of CXL that is oxygen dependent. Our study investigated the effect of increased oxygen availability in epithelium-on CXL on visual acuity and corneal curvature. Methods: We searched PubMed, EMBASE, Medline, Web of Science, and Scopus databases on November 3, 2021. We included studies that reported increased oxygen availability during CXL in patients with keratoconus published within the last 10 years. A meta-analysis on the primary outcomes, maximum keratometry, and corrected distance visual acuity, was conducted. Results: The search yielded 108 publications which were screened and assessed for eligibility. Six studies were included in the systematic review and 5 studies were included in our meta-analysis of the outcomes of increased oxygen availability in accelerated CXL. The meta-analysis on data after 6 months of follow-up found a significant decrease in mean maximum keratometry of 1.2 diopter (95% confidence interval: 0.2–2.3; P=0.02) and an improvement in mean corrected distance visual acuity by 0.08 logMAR (95% confidence interval, 0.02–0.13; P=0.01). There were no serious adverse events reported. Conclusions: Increasing oxygen during epithelium-on CXL improved visual acuity and produced corneal flattening without any serious adverse events in patients with keratoconus. The demarcation line depth was significantly higher with oxygen compared to the control group. Further data are required with a control group and long-term follow-up across a range of CXL protocols for implementation into standard clinical practice.

Aims To investigate myopic maculopathy in Chinese children with high myopia and its association with choroidal and retinal changes. Methods This cross-sectional study included Chinese children aged 4–18 years with high myopia. Myopic maculopathy was classified by fundus photography and retinal thickness (RT) and choroidal thickness (ChT) in the posterior pole were measured by swept-source optical coherence tomography. A receiver operation curve was used to determine the efficacy of fundus factors in classifying myopic maculopathy. Results In total, 579 children aged 12.8±3.2 years with a mean spherical equivalent of −8.44±2.20 D were included. The proportions of tessellated fundus and diffuse chorioretinal atrophy were 43.52% (N=252) and 8.64% (N=50), respectively. Tessellated fundus was associated with a thinner macular ChT (OR=0.968, 95% CI: 0.961 to 0.975, p<0.001) and RT (OR=0.977, 95% CI: 0.959 to 0.996, p=0.016), longer axial length (OR=1.545, 95% CI: 1.198 to 1.991, p=0.001) and older age (OR=1.134, 95% CI: 1.047 to 1.228, p=0.002) and less associated with male children (OR=0.564, 95% CI: 0.348 to 0.914, p=0.020). Only a thinner macular ChT (OR=0.942, 95% CI: 0.926 to 0.959, p<0.001) was independently associated with diffuse chorioretinal atrophy. When using nasal macular ChT for classifying myopic maculopathy, the optimal cut-off value was 129.00 µm (area under the curve (AUC)=0.801) and 83.85 µm (AUC=0.910) for tessellated fundus and diffuse chorioretinal atrophy, respectively. Conclusion A large proportion of highly myopic Chinese children suffer from myopic maculopathy. Nasal macular ChT may serve as a useful index for classifying and assessing paediatric myopic maculopathy. Trial registration number NCT03666052.

Achromatopsia is the most common cone dysfunction syndrome, affecting 1 in 30,000 people. It is an autosomal recessive disorder with a heterogeneous genetic background with variants reported in CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6. Up to 90% of achromatopsia patients harbour mutations in CNGA3 or CNB3, which encode for the alpha and beta subunits of the cone cyclic nucleotide-gated (CNG) channel in cone-specific phototransduction. The condition presents at birth or early infancy with poor visual acuity, nystagmus, photophobia, and colour vision loss in all axes. Multimodal retinal imaging has provided insightful information to characterise achromatopsia patients based on their genotype. There is no FDA-approved treatment for achromatopsia; however, studies have reported several preclinical gene therapies with anatomical and functional improvements reported in vivo. There are currently five gene therapy clinical trials registered for human patients at the phase I/II stage and for CNGA3 or CNGB3 causing achromatopsia. This review aims to discuss the genetics of achromatopsia, genotypic and phenotypic correlations in multimodal retinal imaging, and the developments and challenges in gene therapy clinical trials.