Diffuse Choroidal Atrophy Research Articles

Characteristics of myopic maculopathy in Chinese children and adolescents with high myopia

AimsTo investigate the characteristics of myopic maculopathy among highly myopic Chinese children and adolescents and explore its associated risk factors.MethodsChildren and adolescents aged 7–17 years with spherical equivalent (SE) ≤...

Bruch's Membrane Opening Changes in Eyes With Myopic Macular Degeneration: AIER-SERI Adult High Myopia Study.

The purpose of this study was to assess the choroidal thickness and the Bruch's membrane opening size and their relationship to visual acuity in eyes with myopic macular degeneration (MMD). This was a population-based, cross-sectional study. Patients over the age of 30years with high myopia (spherical equivalent ≤-5 diopters [D]) were recruited. The eyes were grouped according to the International Meta-Analysis for Pathologic Myopia (META-PM) classification based on fundus photographs and diffuse atrophy was subdivided into peripapillary diffuse choroidal atrophy (PDCA) or macular diffuse choroidal atrophy (MDCA). Swept-source optical coherence tomography imaging was performed and then the subfoveal choroidal thickness (SFCT) and Bruch's membrane opening diameter (BMOD) were measured. Of the 470 study participants recruited, 373 patients (691 eyes), with a mean age of 42.8 ± 7.2years, were eligible for the study and included in the analysis. There was no significant difference in SFCT between MDCA and patchy atrophy (M3) groups (P = 1.000), and the BMOD enlarged significantly from no myopic macular lesions to M3 (the P values of multiple comparison tests were all <0.005). Simple linear regression analysis showed that BMOD correlated positively with age (P < 0.001) and axial length (P < 0.001). Multiple linear regression analysis showed that best corrected visual acuity (BCVA) was significantly correlated with age (P = 0.041), axial length (P = 0.001), and BMOD (P = 0.017), but not with SFCT (P = 0.231). The significant variation of BMOD among MMD groups and the correlation between BMOD and BCVA in MMD eyes suggest that BMOD may be an imaging biomarker for monitoring MMD.

The Genetic Confirmation and Clinical Characterization of LOXL3-Associated MYP28: A Common Type of Recessive Extreme High Myopia.

In previous studies, biallelic LOXL3 variants have been shown to cause autosomal recessive Stickler syndrome in one Saudi Arabian family or autosomal recessive early-onset high myopia (eoHM, MYP28) in two Chinese families. The current study aims to elucidate the clinical and genetic features of LOXL3-associated MYP28 in seven new families and two previously published families. LOXL3 variants were detected based on the exome sequencing data of 8389 unrelated probands with various ocular conditions. Biallelic variants were identified through multiple online bioinformatic tools, comparative analysis, and co-segregation analysis. The available clinical data were summarized. Biallelic LOXL3 variants were exclusively identified in nine of 1226 families with eoHM but in none of the 7163 families without eoHM (P= 2.97 × 10-8, Fisher's exact test), including seven new and two previously reported families. Seven pathogenic variants were detected, including one nonsense (c.1765C>T/p.Arg589*), three frameshift (c.39dupG/p.Leu14Alafs*21; c.544delC/p.Leu182Cysfs*3, c.594delG/p.Gln199Lysfs*35), and three missense (c.371G>A/p.Cys124Tyr; c.1051G>A/p.Gly351Arg; c.1669G>A/p.Glu557Lys) variants. Clinical data of nine patients from nine unrelated families revealed myopia at the first visit at about 5 years of age, showing slow progression with age. Visual acuity at the last visit ranged from 0.04 to 0.9 (median age at last visit = 5 years, range 3.5-15 years). High myopic fundus changes, observed in all nine patients, were classified as tessellated fundus (C1) in five patients and diffuse choroidal atrophy (C2) in four patients. Electroretinograms showed mildly reduced cone responses and normal rod responses. Except for high myopia, no other specific features were shared by these patients. Biallelic LOXL3 variants exclusively presenting in nine unrelated patients with eoHM provide firm evidence implicating MYP28, with an estimated prevalence of 7.3 × 10-3 in eoHM and of about 7.3 × 10-5 in the general population for LOXL3-associated eoHM. So far, MYP28 represents a common type of autosomal recessive extreme eoHM, with a frequency comparable to LRPAP1-associated MYP23.

MACULAR SENSITIVITY AND CAPILLARY PERFUSION IN HIGHLY MYOPIC EYES WITH MYOPIC MACULAR DEGENERATION.

To evaluate the interrelationship between macular sensitivity and retinal perfusion density (PD) in eyes with myopic macular degeneration (MMD). One hundred and thirty-eight highly myopic eyes from 82 adult participants were recruited. Macular sensitivity was evaluated using the Microperimeter MP-3. Retinal PD was measured using the PLEX Elite 9000 swept source optical coherence tomography angiography. Macular sensitivity values between different categories of MMD and its relationship with optical coherence tomography angiography measurements were evaluated using multivariable linear mixed models, adjusting for age and axial length. Macular sensitivity reduced with increasing severity of MMD (β ≤ -0.95, P < 0.001), whereas the best-corrected visual acuity was not associated with MMD severity (P > 0.04). Persons who were older (β = -0.08, P < 0.001), with longer axial length (β = -0.32, P = 0.005), presence of macular diffuse choroidal atrophy (β = -2.16, P < 0.001) or worse MMD (β = -5.70, P < 0.001), and presence of macular posterior staphyloma (β ≤ -2.98, P < 0.001) or Fuchs spot (β = -1.58, P = 0.04) were associated with reduced macular sensitivity. Macular sensitivity was significantly associated with deep retinal PD in MMD (β = 0.15, P = 0.004) but not with superficial retinal PD (P = 0.62). There was a strong correlation between reduced macular sensitivity and increasing MMD severity, even in mild MMD independent of the best-corrected visual acuity. Furthermore, macular sensitivity was correlated with deep retinal PD, suggesting a vasculature-function relationship in MMD.

IMI Pathologic Myopia.

Pathologic myopia is a major cause of visual impairment worldwide. Pathologic myopia is distinctly different from high myopia. High myopia is a high degree of myopic refractive error, whereas pathologic myopia is defined by a presence of typical complications in the fundus (posterior staphyloma or myopic maculopathy equal to or more serious than diffuse choroidal atrophy). Pathologic myopia often occurs in eyes with high myopia, however its complications especially posterior staphyloma can also occur in eyes without high myopia.Owing to a recent advance in ocular imaging, an objective and accurate diagnosis of pathologic myopia has become possible. Especially, optical coherence tomography has revealed novel lesions like dome-shaped macula and myopic traction maculopathy. Wide-field optical coherence tomography has succeeded in visualizing the entire extent of large staphylomas. The effectiveness of new therapies for complications have been shown, such as anti-VEGF therapies for myopic macular neovascularization and vitreoretinal surgery for myopic traction maculopathy.Myopia, especially childhood myopia, has been increasing rapidly in the world. In parallel with an increase in myopia, the prevalence of high myopia has also been increasing. However, it remains unclear whether or not pathologic myopia will increase in parallel with an increase of myopia itself. In addition, it has remained unclear whether genes responsible for pathologic myopia are the same as those for myopia in general, or whether pathologic myopia is genetically different from other myopia.

PROGRESSION OF MYOPIC MACULOPATHY IN CHINESE CHILDREN WITH HIGH MYOPIA: A Long-Term Follow-Up Study.

To investigate the progression of myopic maculopathy and associated factors in highly myopic Chinese children. In this retrospective observational case series, biometric fundus features were morphometrically measured on photographs. Myopic maculopathy was defined as recommended by the Meta-analysis of Pathologic Myopia Study Group. The study included 274 children (mean age: 11.7 ± 2.5 years; mean refractive error: -7.66 ± 1.87 diopters [D]) with a mean follow-up of 4.9 ± 1.2 years. Myopic maculopathy progression was detected in 52 eyes (18.9%; 95% confidence interval [CI]: 14.3-23.7%). In multivariable analysis, myopic maculopathy progression was associated with a decrease in refractive error (odds ratio [OR]: 0.72; 95% CI: 0.56-0.92; P < 0.001) (i.e., higher myopization) and enlargement of parapapillary gamma zone (OR: 7.68; 95% CI: 1.63-36.2; P = 0.002). Incident peripapillary diffuse choroidal atrophy, noted in 47 of 236 eyes (20.0%; 95% CI: 14.8-25.2%), was correlated with a decrease in refractive error (OR: 0.70; 95% CI: 0.54-0.92; P = 0.009) (i.e., higher myopization) and greater gamma zone enlargement (OR: 8.28; 95% CI: 1.33-51.7; P = 0.02). Myopia in schoolchildren may have a considerable risk of progressing to myopic maculopathy. Enlargement of parapapillary gamma zone was a main independent risk factor.

Prevalence and predictors of myopic macular degeneration among Asian adults: pooled analysis from the Asian Eye Epidemiology Consortium

AimsTo determine the prevalence and predictors of myopic macular degeneration (MMD) in a consortium of Asian studies.MethodsIndividual-level data from 19 885 participants from four population-based studies, and 1379 highly myopic...

OCT-Based Diagnostic Criteria for Different Stages of Myopic Maculopathy

To analyze the choroidal thickness (CT) of each type of myopic maculopathy, and to establish an OCT-based classification of myopic maculopathy. Retrospective, hospital-based, cross-sectional study. Highly myopic (HM) eyes that were examined by swept-source OCT. The CT was measured at the subfovea and at 3 mm nasal, temporal, superior, and inferior to the fovea. Myopic maculopathy was classified as tessellation, diffuse atrophy, patchy atrophy, and macular atrophy (MA) based on the fundus photographs. Diffuse atrophy was subdivided into peripapillary diffuse choroidal atrophy (PDCA) or macular diffuse choroidal atrophy (MDCA). The CT of each type of myopic maculopathy and cut-off value for diagnosis of diffuse atrophy. We studied 1487 eyes of 884 patients (mean age: 58 years; mean axial length [AxL]: 29.9 mm). Subfoveal CT decreased with an increase in the severity of the myopic maculopathy. The mean subfoveal CT in HM eyes with normal fundus was 274.5 μm, with tessellation was 129.1 μm, with PDCA was 84.6 μm, with MDCA was 50.2 μm, with patchy atrophy was 48.6 μm, with choroidal neovascularization-related MA was 27.3 μm, and with patchy atrophy-related MA was 3.5 μm. Using receiver operating characteristic curves, the optimal CT to predict the presence of PDCA was 56.5 μm nasally, and the CT to predict the presence of MDCA was 62 μm subfoveally. The subfoveal CT was not significantly different in eyes with MDCA and patchy atrophy. A decrease of the subfoveal CT was associated with an older age (P < 0.001), longer AxL (P < 0.001), presence of myopic maculopathy (P < 0.001), and presence of CNV (P= 0.002). A decrease of best-corrected visual acuity was not significantly associated with the subfoveal CT. Progressive and continuous choroidal thinning plays a key role in the progression from no maculopathy to tessellation and to diffuse atrophy. The cut-off value of CT can be used for diagnosing PDCA and MDCA. For progression from MDCA to patchy atrophy, factors other than further choroidal thinning such as Bruch membrane defect may be involved. The subfoveal CT was not a predictor of visual acuity in HM eyes without CNV.

Parapapillary Diffuse Choroidal Atrophy in Children Is Associated With Extreme Thinning of Parapapillary Choroid.

To analyze morphologic features of segmental parapapillary diffuse choroidal atrophy (PDCA) in children. The study group included children (age ≤15 years) with high myopia who attended the Tokyo High Myopia Clinic. Control groups comprised participants of the population-based Gobi Desert Children Eye Study (GobiDCES). Fundus photographs were examined for presence of PDCA and choroidal thickness (CT) was measured by optical coherence tomography. The study group included 41 eyes of 21 children with PDCA (mean age: 9.4 ± 3.7 years; mean refractive error: -11.5 ± 3.1 diopters) and the GobiDCES included 1463 children (age: 11.8 ± 3.5 years). In the study group, all eyes showed an extreme and abrupt thinning of the temporal parapapillary choroid. At 2500 μm nasal to the foveola, CT was <60 μm in 31 (76%) eyes of the study group but in none (0/1463) of the GobiDCES (P < 0.001), except for one child with PDCA. Parapapillary diffuse choroidal atrophy in children is associated with abrupt segmental thinning of the choroid in the temporal parapapillary region, in addition to the thinning of the subfoveal choroid after adjusting for refractive error and age.

Intra-arterial chemotherapy for retinoblastoma: First Indian report.

Aim:To describe treatment outcomes and complications of selective intra-arterial chemotherapy (IAC) for retinoblastoma (RB) in Indian eyes.Materials and Methods:Single center, retrospective interventional case series of 6 eyes with RB who underwent IAC using Melphalan (3 mg/5 mg/7.5 mg) and topetecan (1 mg) (n = 4) or melphalan (3 mg/5 mg/7.5 mg) alone (n = 2) between December 2013 and June 2014. In all, 17 IAC procedures were performed using selective ophthalmic artery cannulation. Treatment outcomes were evaluated in terms of tumor control, vitreous and subretinal seeds control and globe salvage rates.Results:IAC was employed as primary (n = 1) or secondary (n = 5) modality of treatment. Each eye received mean 3 IAC sessions (median: 3; range: 1-4 sessions). Eyes were classified according to international classification of RB as Group B (n = 1), C (n = 1), D (n = 2) and E (n = 2). Following IAC, complete regression of the main tumor was seen in 3 cases (50%), partial regression in 2 (33%), while 1 case (15%) showed no response. Of 4 eyes with subretinal seeds, 1 (25%) eye had complete regression while 3 (75%) eyes had partial regression. Of 5 eyes with vitreous seeds, 2 (40%) eyes had complete regression while 3 (60%) eyes had a partial response. Globe salvage was achieved in 5 of 6 eyes (83%). Diffuse choroidal atrophy and vitreous hemorrhage were observed in 1 (17%) eye, each. No hematologic toxicity or cerebro-vascular events were observed. Mean follow-up period was 5.5 months (median: 6 months, range: 1-6 months).Conclusion:IAC is an effective therapy for globe preservation in eyes with RB. Larger studies with longer follow-up are required to validate these results.

Juvenile glaucoma and optic disc pit with macular detachment in Klinefelter's syndrome

Case reportA 34-year-old man affected by Klinefelter syndrome, with loss of vision in his left eye (LE), ocular hypertension with increased cupping in both eyes, and optic disc pit with serous macular detachment in the LE. Optical coherence tomography showed a macular detachment with a double-layer detachment, consisting of both an inner layer separation and an outer layer detachment. The outer layer detachment did not seem to communicate with the optic disc. DiscussionKlinefelter syndrome has been associated with diffuse choroidal atrophy and colobomas of the iris and choroid. Our patient showed bilateral juvenile glaucoma and unilateral congenital optic disc pit. This association has not been previously reported in the bibliography.

Glaucoma juvenil y foseta papilar con desprendimiento macular asociado a síndrome de Klinefelter

Case reportA 34- year- old man affected by Klinefelter syndrome, with loss of vision in his left eye, ocular hypertension with increased cupping in both eyes, and optic disc pit with serous macular detachment in the left eye. Optical coherence tomography showed a macular detachment with a double-layer detachment, consisting of both an inner layer separation and an outer layer detachment. The outer layer detachment did not seem to communicate with the optic disc. DiscussionKlinefelter syndrome has been associated with diffuse choroidal atrophy and colobomas of the iris and choroid. Our patient showed bilateral juvenile glaucoma and unilateral congenital optic disc pit. This association has not been previously reported in the bibliography.

Ophthalmic pathology in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency caused by the G1528C mutation

Purpose. To define histopathologic features of a recently recognized chorioretinopathy associated with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, a defect of mitochondrial fatty acid oxidation.Methods. Both eyes were obtained at autopsy from a child who died of LCHAD deficiency, caused by the G1528C mutation, at the age of 14 months. Routine histopathology and light microscopic immunohistochemistry were performed, with a panel of 12 antibodies to epithelial, mesenchymal, neuronal, and inflammatory cells, using the avidin-biotinylated peroxidase complex method.Results. The cells of the retinal pigment epithelium (RPE) were rarefied, flattened, and hypopigmented in the posterior pole. The RPE cells reacted normally with MAb Vim 34B to vimentin, and MAb CAM 5.2 and CY-90 for cytokeratin 8 and 18. Scattered among them were many pigment-laden macrophages, reactive with MAb PG-M1. A thin outer nuclear layer in the macular region suggested loss of photoreceptor cells. In routine stainings, patent choriocapillary vessels were sparse. However, a collapsed network of capillaries could be identified by MAb QBEND-10 to the CD34 epitope of vascular endothelial cells. In the peripheral fundus, the RPE and choriocapillaris were normal.Conclusions. The ophthalmopathologic findings corresponded to clinically defined stage 2 of the chorioretinopathy of LCHAD deficiency. Histopathologically, this chorioretinopathy can be classified as diffuse choroidal atrophy with loss of the choriocapillaris. The findings suggest a primary fault at the level of the RPE and choriocapillaris and a secondary macrophage response. Curr. Eye Res. 17: 551–559, 1998.These results were presented in part in the Joint Meeting of the Verboeff Society-European Ophthalmic Pathology Society, Houston, April 1996.

Ocular Pathology of MELAS Syndrome with Mitochondrial DNA Nucleotide 3243 Point Mutation

The authors describe the clinical, histopathologic, and ultrastructural findings in two eyes obtained at autopsy from a 21-year-old woman with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome). The eyes were obtained immediately after death. The right eye was fixed in 10% neutral-buffered formalin and processed for standard histologic examination. The left eye was fixed in a neutral-buffered 2.5% glutaraldehyde solution and processed for transmission electron microscopic examination. The authors compared the histologic and ultrastructural findings with the clinical features recorded photographically. The main clinical ophthalmologic features were bilateral ptosis, chronic external ophthalmoplegia, diffuse choroidal atrophy, atypical pigmentary retinopathy with macular involvement, and patchy atrophy of the iris stroma. Molecular genetic analysis detected a tRNA Leu (UUR) point mutation at position 3243 of mitochondrial DNA (MELAS genotype). Results of histologic and ultrastructural examination showed ragged-red fibers in the rectus muscles, degeneration of photoreceptor outer segments in the macula, hyperpigmentation and atrophy of the retinal pigment epithelium of the macula, atrophy of the iris stroma, early posterior subcapsular cataract, and optic atrophy. The retinal pigment epithelium, inner segments of the photoreceptors, smooth muscle cells of the choroidal and retinal vessels, the dilator and sphincter muscle of the iris, cornea, lens epithelium, and ciliary epithelium all contained many, often enlarged, structurally abnormal mitochondria with occasional paracrystalline inclusions and circular cristae. The MELAS-associated mitochondrial DNA nucleotide 3243 point mutation can cause a spectrum of ocular signs and symptoms that may be dependent on the patient's age and the amount of mutant mitochondrial DNA in the tissue. MELAS syndrome should be considered in the differential diagnosis of bilateral ptosis, external ophthalmoplegia, and atypical pigmentary retinopathy with macular involvement.