Validation of Soft Labels in Developing Deep Learning Algorithms for Detecting Lesions of Myopic Maculopathy From Optical Coherence Tomographic Images.

PURPOSE: It is common for physicians to be uncertain when examining some images. Models trained with human uncertainty could be a help for physicians in diagnosing pathologic myopia. DESIGN: This is a hospital-based study that included 9176 images from 1327 patients that were collected between October 2015 and March 2019. METHODS: All collected images were graded by 21 myopia specialists according to the presence of myopic neovascularization (MNV), myopic traction maculopathy (MTM), and dome-shaped macula (DSM). Hard labels were made by the rule of major wins, while soft labels were possibilities calculated by whole grading results from the different graders. The area under the curve (AUC) of the receiver operating characteristics curve, the area under precision-recall (AUPR) curve, F-score, and least square errors were used to evaluate the performance of the models. RESULTS: The AUC values of models trained by soft labels in MNV, MTM, and DSM models were 0.985, 0.946, and 0.978; and the AUPR values were 0.908, 0.876, and 0.653 respectively. However, 0.56% of MNV "negative" cases were answered as "positive" with high certainty by the hard label model, whereas no case was graded with extreme errors by the soft label model. The same results were found for the MTM (0.95% vs none) and DSM (0.43% vs 0.09%) models. CONCLUSIONS: The predicted possibilities from the models trained by soft labels were close to the results made by myopia specialists. These findings could inspire the novel use of deep learning models in the medical field.

Protection of the Retinal Ganglion Cells: Intravitreal Injection of Resveratrol in Mouse Model of Ocular Hypertension.

Purpose: To investigate the efficacy of intravitreal administration of resveratrol (RSV) in a microbead-induced high intraocular pressure (IOP) murine model for glaucoma. Methods: Experiments were performed using adult C57BL/6JJcl mice. Polystyrene microbeads were injected into the anterior chamber to induce IOP elevation. Retinal flat-mounts and sections were assessed by immunohistochemistry to detect the expression of reactive oxygen species and acetyl-p53 in retinal ganglion cells (RGCs), brain-derived neurotrophic factor (BDNF) in Müller glial cells (MGCs), and the receptor tropomyosin receptor kinase B (TrkB) in RGCs. Light cycler real-time PCR was also used for confirming gene expression of BDNF in primary cultured MGCs exposed to RSV. Results: Microbeads induced high IOP followed by RGC death and axon loss. Administration of RSV rescued RGCs via decreased reactive oxygen species generation and acetyl-p53 expression in RGCs and upregulated BDNF in MGCs and TrkB expression in RGCs, which exhibited a strong cytoprotective action against cell death through multiple pathways under high IOP. Conclusions: Our data suggest that administration of RSV may delay the progress of visual dysfunction during glaucoma and may therefore have therapeutic potential.

Bilateral diffuse retinal pigment epithelium proliferation induced by choroidal inflammation: A case report.

RATIONALE: Proliferation of retinal pigment epithelium (RPE) is typically observed in limited ocular disorders, in connection with the local mechanism of RPE proliferation-mediated wound repair. Bilateral and diffuse type RPE proliferation is considered to be associated with paraneoplastic syndromes, such as a bilateral diffuse uveal melanocytic proliferation. However, other reported diseases that induce bilateral diffuse RPE proliferation are quite rare, especially for patients who are considered to have a non-malignant status. PATIENT CONCERNS: The bilateral eyes of a 47-year-old woman with bilateral ocular inflammation, presented united multiple small to medium white retinal lesions during the disease progress. DIAGNOSES: Optical coherence tomography showed scattered serous retinal detachments, choroidal folds, choroidal thickening and diffuse RPE proliferation. As autofluorescence and angiography showed a "giraffe pattern", bilateral diffuse uveal melanocytic proliferation was suspected. However, systemic investigations identified no malignancy. In consideration of the above findings, choroidal inflammation was thought to be the major cause of this condition. INTERVENTIONS: The patient was administered intensive systemic steroids. Over the next 2 months, the amount of steroid was tapered off. OUTCOMES: After administration, the bilateral diffuse RPE proliferation settled down. During the 2-year follow-up, there was no recurrence of ocular inflammation and diffuse RPE proliferation, or any other malignancy found. LESSONS: This finding demonstrates that bilateral diffuse RPE proliferation can be generated as a secondary phenomenon of choroidal inflammation in patients with a non-malignant status.

Visual arrestin modulates gene expression in the retinal pigment epithelium: Implications for homeostasis in the retina.

The retinal pigment epithelium (RPE) is essential for maintaining retinal homeostasis by removing and recycling photoreceptor outer segment (POS) in membranes. It also produces and secretes growth factors involved in retinal homeostasis. Arrestin 1 (ARR1) is specifically expressed in photoreceptors (PRs) and a vital molecule for keeping visual cycle between PRs and RPE. In the present study, we showed the expression of ARR1 was decreased by form-deprivation (FD) in retina of rat. The ARR1 was detected in the RPE of the controls but not in the RPE of FD, which indicates RPE phagocytes POS containing ARR1. Furthermore, we overexpressed ARR1 in cultured human RPE and revealed the ARR1 upregulates bFGF expression and downregulates TGF-ß1, -ß2 and bone morphogenetic protein-2 (BMP-2). The upregulation of bFGF by ARR1 directly works for PR survival and the downregulation of TGF-ßs by ARR1 inhibits epithelial mesenchymal transition (EMT) of RPE, which is the underlying mechanism of keeping retinal homeostasis. Our results also indicate the regulation of ARR1 expression in RPE might become a novel therapeutic option for various ocular diseases.

OCT-Based Diagnostic Criteria for Different Stages of Myopic Maculopathy.

PURPOSE: To analyze the choroidal thickness (CT) of each type of myopic maculopathy, and to establish an OCT-based classification of myopic maculopathy. DESIGN: Retrospective, hospital-based, cross-sectional study. PARTICIPANTS: Highly myopic (HM) eyes that were examined by swept-source OCT. METHODS: 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). MAIN OUTCOME MEASURES: The CT of each type of myopic maculopathy and cut-off value for diagnosis of diffuse atrophy. RESULTS: 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. CONCLUSIONS: 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.

CLINICAL FEATURES OF LACQUER CRACKS IN EYES WITH PATHOLOGIC MYOPIA.

PURPOSE: To analyze the morphologic features of lacquer cracks (LCs), compare their detectability by different imaging instruments, and determine their progressive pattern. METHODS: The medical records of 47 highly myopic eyes of 33 patients with LCs were reviewed. Fundus fluorescein angiography was used as the primary method of identifying LCs, and the detection rate was compared with that by fundus autofluorescence and optical coherence tomography. RESULTS: A total of 176 LCs were detected in the 47 eyes. Lacquer cracks were detected more frequently in the temporal (44.3%) than the inferior (30.7%), superior (17.0%), and nasal (8.0%) quadrants of the retina. The detection rate of LCs was 98% in fundus photographs and 85% by fundus autofluorescence and optical coherence tomography. A progression of the LCs was observed in 22 of the 41 eyes with a follow-up period of ≥1 year. The progression patterns were an increase in the number (18 of 41, including 5 eyes in which new LCs had a branching pattern), elongation (4 of 41), and progression to patchy atrophy (6 of 41). CONCLUSION: Lacquer cracks can be detected noninvasively by fundus autofluorescence and optical coherence tomography; however, improvements are necessary to detect all of the lesions. Lacquer cracks frequently progress with time, and an increase in the number of LCs was the most frequent progression pattern.

FIVE-YEAR OUTCOMES OF INTRAVITREAL RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH PATHOLOGIC MYOPIA.

PURPOSE: To determine the 5-year outcome of intravitreal ranibizumab (IVR) for myopic choroidal neovascularization (CNV). METHOD: We retrospectively analyzed the medical records of 51 eyes of 51 consecutive patients with myopic CNV who had been treated with IVR with a minimum follow-up period of 5 years after the initial IVR injection. The factors that predicted the best-corrected visual acuity (BCVA) at 5 years after IVR were determined by multiple regression analysis. RESULTS: The mean age of the subjects was 63.6 years, and the mean axial length was 29.4 mm. The mean number of IVR was 1.6, and 34 eyes (66.7%) had only a single IVR. At the baseline and at the 1-year, 2-year, 4-year, and 5-year period, the mean BCVAs were 20/49, 20/37, 20/41, 20/45, and 20/42, respectively. Stepwise multiple regression analysis showed that the BCVA at 5-year period was significantly correlated with the baseline BCVA, the number of IVR injections, and the size of the CNV-related macular atrophy. CONCLUSION: Intravitreal ranibizumab provide a 5-year visual benefit in eyes with myopic CNV compared with the natural course. A lack of enlargement of the CNV-related macular atrophy, a better baseline BCVA, and a minimum number of IVR injections were associated with better visual outcomes.

CORRELATIONS BETWEEN EXPERIMENTAL MYOPIA MODELS AND HUMAN PATHOLOGIC MYOPIA.

PURPOSE: To analyze the hallmark features of pathologic myopia developed in animal models and compare them with those seen in patients. METHODS: A literature review was performed to identify animal models that exhibited key features of pathologic myopia, namely posterior staphyloma, myopic maculopathy, lacquer cracks, and choroidal neovascularization, either spontaneously or induced by monocular deprivation. Using imaging modalities, such as optical coherence tomography, confocal scanning laser ophthalmoscopy, fluorescein angiography, and electron microscopy, these features were compared with those found in myopic maculopathy of patients. RESULTS: Three types of animals were identified. The LRP2 knockout mice exhibited posterior staphylomas and chorioretinal atrophy at 21 and 60 days after birth, respectively. Retinopathy globe enlarged (rge) chicks and normal lid-sutured chicks developed lacquer cracks and chorioretinal atrophy. Lacquer cracks detected in rge chicks subsequently progressed to patchy chorioretinal atrophy, which is also commonly seen in patients with pathologic myopia. CONCLUSION: The LRP2 knockout mice, retinopathy globe enlarged (rge) chicks, and normal lid-sutured chicks exhibit features typical for myopic maculopathy in patients and could serve to further elucidate the pathogenesis of myopic maculopathy.

CCDC102B confers risk of low vision and blindness in high myopia.

The incidence of high myopia is increasing worldwide with myopic maculopathy, a complication of myopia, often progressing to blindness. Our two-stage genome-wide association study of myopic maculopathy identifies a susceptibility locus at rs11873439 in an intron of CCDC102B (P = 1.77 × 10-12 and Pcorr = 1.61 × 10-10). In contrast, this SNP is not significantly associated with myopia itself. The association between rs11873439 and myopic maculopathy is further confirmed in 2317 highly myopic patients (P = 2.40 × 10-6 and Pcorr = 1.72 × 10-4). CCDC102B is strongly expressed in the retinal pigment epithelium and choroids, where atrophic changes initially occur in myopic maculopathy. The development of myopic maculopathy thus likely exhibits a unique background apart from the development of myopia itself; elucidation of the roles of CCDC102B in myopic maculopathy development may thus provide insights into preventive methods for blindness in patients with high myopia.

Progression of Myopic Maculopathy during 18-Year Follow-up.

PURPOSE: To examine the progression pattern of myopic maculopathy. DESIGN: Retrospective, observational case series. PARTICIPANTS: Highly myopic patients who had been followed up for 10 years or more. METHODS: Using fundus photographs, myopic features were differentiated according to Meta-analysis of Pathologic Myopia (META-PM) Study Group recommendations. MAIN OUTCOME MEASURES: Progression pattern of maculopathy. RESULTS: The study included 810 eyes of 432 patients (mean age, 42.3±16.8 years; mean axial length, 28.8±1.9 mm; mean follow-up, 18.7±7.1 years). The progression rate of myopic maculopathy was 47.0 per 1000 eye-years. Within the pathologic myopia (PM) group (n = 521 eyes), progression of myopic maculopathy was associated with female gender (odds ratio [OR], 2.21; P = 0.001), older age (OR, 1.03; P = 0.002), longer axial length (OR, 1.20; P = 0.007), greater axial elongation (OR, 1.45; P = 0.005), and development of parapapillary atrophy (PPA; OR, 3.14; P < 0.001). Diffuse atrophy, found in 217 eyes without choroidal neovascularization (CNV) or lacquer cracks (LCs) at baseline, progressed in 111 (51%) eyes, leading to macular diffuse atrophy (n = 64; 64/111 or 58%), patchy atrophy (n = 59; 53%), myopic CNV (n = 18; 16%), LCs (n = 9; 5%), and patchy-related macular atrophy (n = 3; 3%). Patchy atrophy, detected in 63 eyes without CNV or LCs at baseline, showed progression in 60 eyes (95%), leading to enlargement of original patchy atrophy (n = 59; 59/60 or 98%), new patchy atrophy (n = 29; 48%), CNV-related macular atrophy (n = 13; 22%), and patchy-related macular atrophy (n = 5; 8%). Of 66 eyes with LCs, 43 eyes (65%) showed progression with development of new patchy atrophy (n = 38; 38/43 or 88%) and new LCs (n = 7; 16%). Reduction in best-corrected visual acuity (BCVA) was associated mainly (all P < 0.001) with the development of CNV or CNV-related macular atrophy and enlargement of macular atrophy. CONCLUSIONS: The most frequent progression patterns were an extension of peripapillary diffuse atrophy to macular diffuse atrophy in diffuse atrophy, enlargement of the original atrophic lesion in patchy atrophy, and development of patchy atrophy in LCs. Main risk factors for progression were older age, longer axial length, and development of PPA.

TEMPORAL VASCULAR ARCADE WIDTH AND ANGLE IN HIGH AXIAL MYOPIA.

PURPOSE: Axial myopia is associated with elongation of the posterior ocular segment. The authors measured posterior fundus landmarks and assessed their associations with axial length. METHODS: Using fundus photographs, the authors measured the vertical distance between the temporal superior and temporal inferior arterial arcade (VDA) and the angle kappa between the temporal arterial arcades among other morphometric variables. RESULTS: The study included 456 eyes with a mean age of 61.2 ± 14.2 years (range: 13-88 years) and mean axial length of 29.4 ± 2.1 mm (range: 23.2-35.3 mm). Mean angle kappa was 91.3 ± 17.2° (range: 39-161°), and mean VDA was 7.93 ± 1.71 mm (range: 2.72-12.85 mm). In multivariate regression analysis, wider angle kappa was associated (regression coefficient r: 0.47) with shorter axial length (P = 0.002; beta: -0.17; B: -1.37; 95% confidence interval [CI]:-2.23 to -0.51), longer VDA (P < 0.001; beta: 0.27; B: 2.70; 95% CI: 1.85-3.54), shorter disk-foveola distance (P < 0.001; beta: -0.22; B: -4.76; 95% CI: -7.05 to -2.46), shorter vertical optic disk diameter (P = 0.002; beta: -0.14; B: -6.83; 95% CI: -11.1 to -2.56), lower number of any chorioretinal lesions (P = 0.007; beta: -0.13; B: -2.11; 95% CI: -3.63 to -0.58), and longer maximal vertical chorioretinal lesion diameter (P = 0.05; beta: 0.09; B: 0.92; 95% CI: -0.02 to 1.86). A longer VDA was associated (r: 0.31) with longer axial length (P < 0.001; beta: 0.22; B: 0.18; 95% CI: 0.10-0.25), wider angle kappa (P < 0.001; beta: 0.28; B: 0.03; 95% CI: 0.02-0.04) and higher number of chorioretinal lesions (P = 0.03; beta: 0.10; B: 0.16; 95% CI: 0.02-0.31). If eyes with chorioretinal lesions were excluded, the association between longer VDA and longer axial length was no longer statistically significant (P > 0.10). CONCLUSION: Axial elongation was correlated with decreasing angle kappa, caused by an elongation of the disk-foveola distance because of an enlargement of the gamma zone, whereas VDA remained constant. By contrast, horizontal length of macular Bruch membrane and vertical length of macular Bruch membrane were independent of axial elongation. Axial elongation did not lead to lengthening of Bruch membrane in the macular region in eyes without macular chorioretinal lesions.

Establishment of novel therapy to reduce progression of myopia in rats with experimental myopia by fibroblast transplantation on sclera.

Myopia is one of the most common visual disorders, and is characterized by a progressive axial elongation of the eye. Several methods have been tried to reduce the progression of axial elongation and myopia, but there are still no well-accepted procedures. We hypothesized that transplantation of fibroblasts on the sclera would lead to the synthesis of collagen fibrils on the sclera and reinforce it, and reduce the degree of axial elongation of eyes with form deprivation myopia. To examine this, we developed a form deprivation myopia model in albino Wistar rats and examined the effects of human fibroblasts (hFbs) transplantation on the sclera in the progression of myopia and axial elongation. We found that the form deprivation by eyelid suture induced a myopic shift and axial elongation associated with a thinner sclera and smaller-diameter collagen fibrils in Wistar rats. We also found that the transplanted hFbs synthesized type 1 collagen fibrils on the rat sclera, and these eyes with form deprivation had significantly reduced ocular elongation and myopic shift than the eyes without hFbs transplantation. Some of the synthesized collagen fibrils migrated into the sclera and had a bundle-like appearance and a stripe-like pattern, indicating they had mature characteristics. These findings suggest that the rat sclera was reinforced by the newly synthesized collagen fibrils and the axial elongation was reduced. These results can provide important information for the development of a therapy targeting myopia in humans. Copyright © 2017 John Wiley & Sons, Ltd.

Intraocular Pressure and Glaucomatous Optic Neuropathy in High Myopia.

Purpose: To examine the association between intraocular pressure (IOP) and the prevalence of glaucomatous optic neuropathy (GON) in high myopia. Methods: The hospital-based observational study consisted of patients treated in the Tokyo High Myopia Clinics and for whom fundus photographs and IOP readings were available. The appearance of the optic nerve head on fundus photographs was the basis for the definition of GON. Results: Among 517 eyes of 261 patients (mean age: 62.1 ± 14.2 years; range: 13-89 years; mean axial length: 29.5 ± 2.2 mm; range: 23.2-35.3 mm), GON was present in 141 eyes (27.3%; 95% confidence intervals [CIs]: 23.4, 31.0). Mean IOP did not differ significantly (P = 0.53) between the glaucoma group (14.5 ± 3.3 mm Hg; median: 14 mm Hg; range: 8-38 mm Hg) and the nonglaucomatous group (14.7 ± 2.5 mm Hg; median: 14 mm Hg; range: 6-23 mm Hg). In eyes with an axial length of ≤27.4 mm, higher presence of GON was correlated only with higher IOP (P = 0.037; odds ratio [OR]:1.35; 95% CI: 1.02, 1.80). In eyes with an axial length of ≥27.5 mm, presence of GON was correlated with older age (P < 0.001; OR: 1.05; 95% CI :1.03, 1.08), longer axial length (P < 0.001; OR: 1.60; 95% CI: 1.34, 1.91), shorter vertical diameter of the temporal arterial arcade (P = 0.009; OR: 0.82; 95% CI: 0.71, 0.95), and longer minimal optic disc diameter (P = 0.002; OR: 3.07; 95% CI: 1.52, 6.21). If IOP was added to the model, it was not significantly associated with the prevalence of GON (P = 0.97; OR: 1.00; 95% CI: 0.91, 1.10). Conclusions: GON was associated with elevated IOP in myopic eyes with an axial length of ≤27.4 mm, while in more highly myopic eyes (axial length ≥27.5 mm), larger optic disc, longer axial elongation and older age-but not IOP mostly within its normal range-were factors associated with GON. Future studies may examine an abnormally low IOP to be associated with a lower GON prevalence in highly myopic eyes.

Glaucoma in high myopia and parapapillary delta zone.

PURPOSE: To examine the prevalence of glaucomatous optic neuropathy (GON) in a medium myopic to highly myopic group of patients and its association with parapapillary gamma zone and parapapillary delta zone. METHODS: The retrospective observational hospital-based study included patients who had attended the Tokyo High Myopia Clinics within January 2012 and December 2012 and for whom fundus photographs were available. GON was defined based on the appearance of the optic nerve head on the fundus photographs. RESULTS: The study included 519 eyes (262 individuals) with a mean age of 62.0±14.3 years (range:13-89 years) and mean axial length of 29.5±2.2 mm (range:23.2-35.3mm). GON was present in 141 (27.2%; 95% confidence intervals (CI): 23.3, 31.0%) eyes. Prevalence of GON increased from 12.2% (1.7, 22.7) in eyes with an axial length of <26.5mm to 28.5% (24.4, 32.5) in eyes with an axial length of ≥26.5mm, to 32.6% (27.9, 37.2) in eyes with an axial length of ≥28mm, to 36.0% (30.5, 41.4) in eyes with an axial length of ≥29mm, and GON prevalence increased to 42.1% (35.5, 48.8) in eyes with an axial length of ≥30mm. In multivariate analysis, higher GON prevalence was associated (Nagelkerke r2: 0.28) with larger parapapillary delta zone diameter (P<0.001; odds ratio (OR):1.86;95%CI:1.33,2.61), longer axial length (P<0.001;OR:1.45;95%CI:1.26,1.67) and older age (P = 0.01;OR:1.03;95%CI:1.01,1.05). If parapapillary delta zone width was replaced by the vertical disc diameter, higher GON prevalence was associated (r2:0.24) with larger vertical optic disc diameter (P = 0.04;OR:1.70;95%CI:1.03,2.81), after adjusting for longer axial length (P<0.001;OR:1.44;95%CI:1.26,1.64) and older age (P<0.001;OR:1.04;95%CI:1.02,1.06). CONCLUSIONS: Axial elongation associated increase in GON prevalence (mean: 28.1% in a medium to highly myopic study population) was associated with parapapillary delta zone as surrogate for an elongated peripapillary scleral flange and with larger optic disc size.

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

Purpose: To analyze morphologic features of segmental parapapillary diffuse choroidal atrophy (PDCA) in children. Methods: 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. Results: 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. Conclusions: 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.

SIX-YEAR OUTCOMES OF INTRAVITREAL BEVACIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH PATHOLOGIC MYOPIA.

PURPOSE: To investigate the 6-year outcome of intravitreal bevacizumab (IVB) to treat eyes with active choroidal neovascularization (CNV) due to pathologic myopia. METHODS: Medical records of 36 eyes of 35 consecutive patients with high myopia (refractive error ≥8 D or axial length ≥26.5 mm) and active CNV, who had been treated with IVB and followed for ≥6 years were analyzed. The factors that predicted the best-corrected visual acuity (BCVA) at 6 years after IVB were determined by multiple regression analyses. RESULTS: The mean age of the subjects was 58 years, and the mean axial length was 29 mm. Twenty-one eyes had subfoveal CNV and 15 eyes had nonsubfoveal CNV. During the 6-year follow-up, the mean number of IVB was 1.78. The mean BCVA logMAR (equivalent Snellen visual acuity) was 0.50 (20/63), 0.31 (20/40), 0.39 (20/50), and 0.45 (20/63) at the baseline, and at 2, 4, and 6 years after the IVB. The BCVA was significantly improved at 2 and 4 years compared with baseline values but not at 6 years. Stepwise multiple regression analyses showed that the BVCA at 6 years was significantly correlated with the size of the CNV-related macular atrophy, and the baseline BCVA and CNV size. CONCLUSION: The significant correlation between the BCVA at 6 years and the size of the macular atrophy indicates that treatments to prevent the development of macular atrophy are important for the long-term visual outcome in eyes with active CNV.

Peripapillary Diffuse Chorioretinal Atrophy in Children as a Sign of Eventual Pathologic Myopia in Adults.

PURPOSE: To search for a morphologic biomarker to differentiate between pathologic myopia and simple childhood myopia. DESIGN: Retrospective case series. PARTICIPANTS: The study included children (age ≤15 years) with high myopia (as defined by the Japanese Ministry of Health and Welfare) who attended the High Myopia Clinic between April 1982 and March 1994, had undergone fundus photography, and had a follow-up of 20 years or more. METHODS: Fundus photographs obtained in childhood and adulthood were examined for presence of pathologic myopia, defined by high myopia (myopic refractive error >8 diopters or axial length ≥26.5 mm) and the presence of stage 2 or higher myopic maculopathy. MAIN OUTCOME MEASURES: Myopic maculopathy in childhood. RESULTS: The study included 56 eyes of 29 patients with a mean age of 10.2±3.6 years at the initial visit and an age of 36.0±7.6 years at the last visit. Mean axial length was 27.0±1.4 mm at baseline and 29.7±2.0 mm at the last visit. At the last visit, 19 eyes (34%) had tessellated fundus alone, 31 eyes (55%) had diffuse chorioretinal atrophy, 3 eyes (5%) showed patchy chorioretinal atrophy, and 1 eye (2%) had macular atrophy. Thus, 35 eyes (63%) had pathologic myopia in adulthood. Among the 35 eyes, 29 (83%) already had diffuse chorioretinal atrophy at the initial visit in childhood and the remaining 6 eyes (17%) showed tessellated fundus in childhood. The diffuse chorioretinal atrophy seen in childhood was restricted to the area temporal to the peripapillary region. CONCLUSIONS: The presence of peripapillary diffuse chorioretinal atrophy in children with high axial myopia may be an indicator for the eventual development of advanced myopic chorioretinal atrophy in later life. These features in children may be helpful for differentiating simple childhood myopia from eventual pathologic myopia.

Glaucomatous-Type Optic Discs in High Myopia.

PURPOSE: To assess the prevalence of glaucoma in patients with high myopia defined as myopic refractive error of >-8 diopters or axial length ≥26.5 mm. METHODS: The hospital-based observational study included 172 patients (336 eyes) with a mean age of 61.9±12.3 years and mean axial length of 30.1±2.3 mm (range: 24.7-39.1mm). Glaucomatous-type optic discs were defined by glaucomatous optic disc appearance. Glaucoma was defined by glaucomatous optic disc appearance and glaucomatous Goldmann visual field defects not corresponding with myopic macular changes. RESULTS: Larger disc area (mean: 3.18±1.94 mm2) was associated with longer axial length (P<0.001; standardized correlation coefficient: 0.45). Glaucoma was detected in 94 (28%; 95% Confidence intervals: 23%, 33%) eyes. In multivariate analysis, glaucoma prevalence was 3.2 times higher (P<0.001) in megalodiscs (>3.79 mm2) than in normal-sized discs or small discs (<1.51 mm2) after adjusting for older age. Axial length was not significantly (P = 0.38) associated with glaucoma prevalence in that model. Glaucoma prevalence increased by a factor of 1.39 for each increase in optic disc area by one mm2. Again, axial length was not significantly (P = 0.38) associated with glaucoma prevalence when added to this multivariate model. CONCLUSION: Within highly myopic individuals, glaucoma prevalence increased with larger optic disc size beyond a disc area of 3.8 mm2. Highly myopic megalodiscs as compared to normal sized discs or small discs had a 3.2 times higher risk for glaucomatous optic nerve neuropathy. The increased glaucoma prevalence in axial high myopia was primarily associated with axial myopia associated disc enlargement and not with axial elongation itself.

Comparison of Clinical Features in Highly Myopic Eyes with and without a Dome-Shaped Macula.

PURPOSE: To compare the clinical features of highly myopic eyes with a dome-shaped macula (DSM) with those without a DSM and to identify the funduscopic clues to suspect the presence of DSM. DESIGN: Retrospective case series. PATIENTS: A total of 586 patients (1118 eyes) with high myopia (refractive error <-8 diopters [D] or axial length ≥26.5 mm) who had optical coherence tomography (OCT) examinations through the central fovea at our High Myopia Clinic between February 2012 and November 2013. METHODS: Vertical and horizontal OCT scans across the central fovea were retrospectively analyzed. A DSM was defined by the presence of an inward bulge of >50 µm in the vertical OCT image. Fundus photographs also were analyzed to identify the funduscopic clues to suspect the presence of DSM. MAIN OUTCOME MEASURES: The rate of DSM in 1118 highly myopic eyes. The rate of DSM in highly myopic eyes with macular complications. Funduscopic features to suggest the presence of DSM. RESULTS: Among the 1118 eyes, 225 (20.1%) had a DSM. A DSM was present in both vertical and horizontal OCT sections in 20% of eyes, along only the vertical section in 77% of eyes, and in only the horizontal section in 2% of eyes. The results of multiple regression analyses showed that serous retinal detachment and foveal and extrafoveal retinoschisis were significantly associated with the presence of DSM and that choroidal neovascularization was not. Ophthalmoscopically, 91.4% of the eyes with the appearance of a horizontal ridge connecting the optic disc and the fovea had a DSM. CONCLUSIONS: A DSM is found in as many as 20% of highly myopic individuals. Horizontal ridges connecting the optic disc and the fovea might be an important clue to suspect the presence of a DSM on the basis of fundus photographs.

Changes of axial length measured by IOL master during 2 years in eyes of adults with pathologic myopia.

OBJECTIVE: To examine the change of the axial length measured by IOL Master in adults with high myopia during a 2-year period. DESIGN: Open-label, consecutive, prospective longitudinal case series. METHODS: One hundred and eighty-five eyes of 185 consecutive patients with bilateral high myopia (myopia ≤ -6 diopters (D) or axial length ≥ 26.5 mm) were studied. The mean age of the patients was 48.4 ± 12.2 years, with a range of 22 to 84 years. The axial length, the anterior chamber depth, and the radius of curvature of the cornea were measured by IOL Master at the initial examination and at 2 years after the first visit. The significance of the changes in the axial length after the 2-year periods was determined. Multiple regression analyses were performed to identify the factors which were significantly associated with the increase of the axial length. RESULTS: The mean axial length increased significantly from 29.35 ± 1.80 mm to 29.48 ± 1.85 mm in 2 years, a mean increase of 0.13 mm with a range of -0.12 to 1.10 mm. The difference in the increase of the axial length between the patients with and without a posterior staphyloma was not significant. Among the possible explanatory factors, age, axial length, anterior chamber depth, the radius of curvature of the cornea, and intraocular pressure at the initial examination, the increase in the axial length was significantly and positively correlated with the axial length at the initial examination. CONCLUSIONS: The measurement by IOL Master in a large population of highly myopic patients clearly showed that the axial length continued to increase in a span of 2 years even in the 4th decade of life. The eyes with longer axial length showed a greater increase of axial length, suggesting the possibility that the more myopic eyes become more myopic with increasing age.