Defects in Membrane Frizzled-related Protein (MFRP) cause autosomal recessive retinitis pigmentosa (RP). MFRP codes for a retinal pigment epithelium (RPE)-specific membrane receptor of unknown function. In patient-specific induced pluripotent stem (iPS)-derived RPE cells, precise levels of MFRP, and its dicistronic partner CTRP5, are critical to the regulation of actin organization. Overexpression of CTRP5 in naïve human RPE cells phenocopied behavior of MFRP-deficient patient RPE (iPS-RPE) cells. AAV8 (Y733F) vector expressing human MFRP rescued the actin disorganization phenotype and restored apical microvilli in patient-specific iPS-RPE cell lines. As a result, AAV-treated MFRP mutant iPS-RPE recovered pigmentation and transepithelial resistance. The efficacy of AAV-mediated gene therapy was also evaluated in Mfrp^rd6/Mfrp^rd6 mice—an established preclinical model of RP—and long-term improvement in visual function was observed in AAV-Mfrp-treated mice. This report is the first to indicate the successful use of human iPS-RPE cells as a recipient for gene therapy. The observed favorable response to gene therapy in both patient-specific cell lines, and the Mfrp^rd6/Mfrp^rd6 preclinical model suggests that this form of degeneration caused by MFRP mutations is a potential target for interventional trials.

Pathologic myopia is a severe form of myopia that can lead to permanent visual impairment. The recent global increase in the prevalence of myopia has been projected to lead to a higher incidence of pathologic myopia in the future. Thus, imaging myopic eyes to detect early pathological changes, or predict myopia progression to allow for early intervention, has become a key priority. Recent advances in optical coherence tomography (OCT) have contributed to the new grading system for myopic maculopathy and myopic traction maculopathy, which may improve phenotyping and thus, clinical management. Widefield fundus and OCT imaging has improved the detection of posterior staphyloma. Non-invasive OCT angiography has enabled depth-resolved imaging for myopic choroidal neovascularisation. Artificial intelligence (AI) has shown great performance in detecting pathologic myopia and the identification of myopia-associated complications. These advances in imaging with adjunctive AI analysis may lead to improvements in monitoring disease progression or guiding treatments. In this review, we provide an update on the classification of pathologic myopia, how imaging has improved clinical evaluation and management of myopia-associated complications, and the recent development of AI algorithms to aid the detection and classification of pathologic myopia.

Purpose To investigate the predictive factors for myopic macular degeneration (MMD) and progression in adults with myopia. Methods We examined 828 Malay and Indian adults (1579 myopic eyes) with myopia (spherical equivalent (SE) ≤–0.5 dioptres) at baseline who participated in both baseline and 12-year follow-up visits of the Singapore Malay Eye Study and the Singapore Indian Eye Study. Eye examinations, including subjective refraction and axial length (AL) measurements, were performed. MMD was graded from fundus photographs following the Meta-Analysis for Pathologic Myopia classification. The predictive factors for MMD development and progression were assessed in adults without and with MMD at baseline, respectively as risk ratios (RR) using multivariable modified Poisson regression models. The receiver operating characteristic curve was used to visualise the performance of the predictive models for the development of MMD, with performance quantified by the area under the curve (AUC). Results The 12-year cumulative MMD incidence was 10.3% (95% CI 8.9% to 12.0%) among 1504 myopic eyes without MMD at baseline. Tessellated fundus was a major predictor of MMD (RR=2.50, p<0.001), among other factors including age, worse SE and longer AL (all p<0.001). The AUC for prediction of MMD development was found to be 0.78 (95% CI 0.76 to 0.80) for tessellated fundus and increased significantly to an AUC of 0.86 (95% CI 0.84 to 0.88) with the combination of tessellated fundus with age, race, gender and SE (p<0.001). Older age (p=0.02), worse SE (p<0.001) and longer AL (p<0.001) were found to be predictors of MMD progression. Conclusions In adults with myopia without MMD, tessellated fundus, age, SE and AL had good predictive value for incident MMD. In adults with MMD, 1 in 10 eyes experienced progression over the same period. Older age, more severe myopia and longer AL were independent risk factors for progression.

Purpose: The purpose of this study was to assess optic nerve head (ONH) deformations following acute intraocular pressure (IOP) elevations and horizontal eye movements in control eyes, highly myopic (HM) eyes, HM eyes with glaucoma (HMG), and eyes with pathologic myopia (PM) alone or PM with staphyloma (PM + S). Methods: We studied 282 eyes, comprising of 99 controls (between +2.75 and −2.75 diopters), 51 HM (< −5 diopters), 35 HMG, 21 PM, and 75 PM + S eyes. For each eye, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze, (2) 20 degrees adduction, (3) 20 degrees abduction, and (4) primary gaze with acute IOP elevation (to ∼35 mm Hg) achieved through ophthalmodynamometry. We then computed IOP- and gaze-induced ONH displacements and effective strains. Effective strains were compared across groups. Results: Under IOP elevation, we found that HM eyes exhibited significantly lower strains (3.9 ± 2.4%) than PM eyes (6.9 ± 5.0%, P < 0.001), HMG eyes (4.7 ± 1.8%, P = 0.04), and PM + S eyes (7.0 ± 5.2%, P < 0.001). Under adduction, we found that HM eyes exhibited significantly lower strains (4.8% ± 2.7%) than PM + S eyes (6.0 ± 3.1%, P = 0.02). We also found that eyes with higher axial length were associated with higher strains. Conclusions: Our study revealed that eyes with HMG experienced significantly greater strains under IOP compared to eyes with HM. Furthermore, eyes with PM + S had the highest strains on the ONH of all groups.

Purpose To investigate the characteristics, risk factors and visual impact of myopic traction maculopathy (MTM) among adults with myopia in Singapore. Methods We analysed 3316 myopic eyes of adults aged over 40 years who participated in the Singapore Epidemiology of Eye Diseases-2 study. Detailed questionnaires and ophthalmic examinations were conducted. A total of 2913 myopic eyes of 1639 subjects were graded for MTM by spectral-domain optical coherence tomography. MTM is defined as the presence of retinoschisis, lamellar or full-thickness macula hole and foveal retinal detachment. Fundus photographs were graded for myopic macular degeneration (MMD). Results Of these 2913 myopic eyes, the mean and SD of age was 60.1±8.0 years; the spherical equivalent (SE) was −2.5±2.3 D; and the axial length (AL) was 24.6±1.3 mm. MTM was found in 0.9% of myopic eyes and 7.3% of highly myopic eyes. In the multivariate analysis, myopic SE (p<0.001), longer AL (p<0.001), MMD (p=0.01) and epiretinal traction (p<0.001) were independent risk factors for MTM. MTM was not associated with age (p=0.38). MTM was significantly associated with poorer best-corrected visual acuity (BCVA) (p<0.01). Conclusions Our population-based study revealed that MTM was present in 0.9% of myopic eyes and 7.3% of highly myopic eyes. While greater myopic SE, longer AL, MMD and epiretinal traction are risk factors of MTM, age was not related to MTM. MTM has a negative effect on BCVA.