Effect of Low-Concentration Atropine Eye Drops on Parapapillary Gamma Zone Development and Enlargement over 3 Years: The LAMP Study.

To examine histomorphometrically the macular region of highly myopic eyes. On horizontal anterior-posterior histological sections, we examined the posterior pole of 138 human globes (axial length: 20-35 mm). In the parapapillary region, we differentiated between the beta zone (Bruch's membrane without RPE), gamma zone (parapapillary region without Bruch's membrane), and delta zone (elongated and thinned gamma zone). In 12 (8.7%) eyes, a macular Bruch's membrane defect (MBMD) was detected. The MBMD showed a complete lack of RPE and choriocapillaris, and an almost complete lack of photoreceptors. Presence of MBMD was associated with longer axial length (P < 0.001), longer gamma zone (P = 0.04) and delta zone (P < 0.001), thinner peripapillary scleral flange, and thinner sclera just outside of the optic nerve meninges (P < 0.001) and at the posterior pole (P < 0.001). An MBMD was found only in eyes with an axial length of 27 mm or longer. MBMD prevalence in highly myopic eyes was 12/39 or 30.8%. MBMD presence was not significantly related to length of beta zone (P = 0.09). In multivariate binary regression analysis, MBMD presence was significantly (P < 0.001) associated only with axial length. Highly myopic eyes (axial length ≥27mm) can show an MBMD associated with complete loss of RPE and choriocapillaris, and marked reduction of photoreceptors and large choroidal vessels. MBMD presence was strongly associated with axial length and indirectly with parapapillary gamma zone and delta zone. The myopia-associated secondary MBMDs may occur parallel to the myopia-associated widening of Bruch's membrane opening around the optic nerve head.

BackgroundMyopic axial elongation may be due to an equatorial enlargement of Bruch’s membrane (BM), leading to a prolate eye shape and increasing strain with BM and the retinal pigment epithelium (RPE) layer at the posterior pole. The increased BM strain may cause an enlargement of Bruch’s membrane opening (BMO) of the optic nerve head, with the subsequent development and enlargement of parapapillary gamma zone as BM-free parapapillary zone. The increased strain within BM and RPE may also cause lacquer cracks (LCs) as linear breaks in the RPE and / or BM. Studies suggested that a more marked gamma zone enlargement is associated with lower prevalence of LCs or macular BM defects. Here report on the disappearance of a LC during a 10-year follow-up of a highly myopic eye, concurrent with a marked increase in gamma zone.Case presentationA 56-year-old woman showed in her right eye (axial length measured 30.69 mm) a LC, vertically oval optic disc, and parapapillary gamma zone in 2001. When re-examined in 2006, gamma zone had enlarged, while the LC was no longer detectable. In 2011, the LC was not visible neither upon ophthalmoscopy and or upon optical coherence tomography (OCT), while gamma zone had further enlarged. The gamma zone enlargement occurred in a direction perpendicular to the direction of the former LC.ConclusionsThe observation suggest that a LC can decrease in width, in temporal association with an enlargement of gamma zone. It fits with the notion that an enlargement of the BMO (i.e., enlarging gamma zone) may lead to a relaxation of the BM strain and subsequently to a decrease in the width of the LC.

The purpose of this study was to evaluate the associations of optic nerve head (ONH) metrics and parapapillary gamma zone with myopia onset and progression in school children aged 6 to 8 years over a 3-year period. The ONH was imaged by spectral domain-optical coherence tomography (SD-OCT) using an adopted scan protocol comprising 24 equally spaced radial B-scans. The study included 765 children (mean age = 7.69 ± 1.01 years, range = 6-8 years, refractive error = 0.33 ± 1.30 diopters [D] at baseline). Significant differences were found in disc ovality index, gamma zone area, Bruch's membrane opening distance (BMOD), temporal border tissue angle (BTA), and optic disc-fovea distance (DFD) across different refractive status groups (all P < 0.001). Multivariable logistic regression analysis indicated that female sex (odds ratio [OR] = 1.74, P = 0.006), longer axial length (OR = 1.81, P < 0.001), larger nasal BTA (OR = 1.01, P = 0.005), larger temporal BTA (OR = 1.01, P = 0.019), optic disc torsion (OR = 2.12, P = 0.007), and longer DFD at baseline (OR = 3.39, P < 0.001) were risk factors of myopia onset, whereas the presence of the gamma zone at baseline was not. In multivariable linear regression analysis, baseline disc ovality index, BMOD, nasal BTA, temporal BTA, and DFD, as well as changes in BMOD, nasal BTA, temporal BTA, gamma zone area, and DFD were significantly associated with spherical equivalent (SE) progression over 3 years. ONH parameters like nasal BTA, temporal BTA, disc torsion, and DFD may have predictive value for myopia onset and progression. As the myopic SE progresses, gamma zone enlargement coincides with the elongation of BMOD and DFD. It may be explained by an axial elongation-related Bruch's membrane opening shift into the temporal direction.

PII: S1529-1839(05)70297-9

Optic nerve head anatomy in myopia and glaucoma, including parapapillary zones alpha, beta, gamma and delta: Histology and clinical features.

To assess axial elongation-associated characteristics in Bruch's membrane opening (BMO) as the inner optic nerve head lamella. Participants of the population-based Beijing Eye Study without glaucoma underwent optical coherence tomography for measurement of the BMO size and shape. The study included 365 individuals (mean age, 61.0 ± 8.7 years; range, 50-88 years; axial length, 24.45 ± 1.99 mm; range, 21.32-30.88 mm). Larger horizontal (mean:1.62 ± 0.28 mm) and vertical (mean: 1.74 ± 0.27 mm) BMO diameters were linearly associated with longer axial length beyond an axial length of 26.0 mm (horizontal diameter: P < 0.001; standardized regression coefficient β: 0.66; nonstandardized regression coefficient B: 0.22; 95% confidence interval (CI): 0.16, 0.27; vertical diameter: P < 0.001; β: 40; B: 0.12; 95% CI: 0.06, 0.18). In multivariable analysis, wider largest gamma zone was associated with larger intrapapillary Bruch's membrane (BM) overhanging on the side opposite to the largest gamma zone (P = 0.006; β: 0.14; B: 0.35; 95% CI: 0.10, 0.60) and with longer horizontal BMO diameter (P < 0.001; β: 0.46; B: 0.59; 95% CI: 0.46, 0.73). The widest BM overhanging location (superior to nasal) was inversely correlated with the widest gamma zone location (inferior to temporal). Within the axial length group of ≥28.0 mm, eyes with macular BM defects had a less markedly increased BMO than those without macular BM defects (2.27 ± 0.18 vs. 2.71 ± 0.41 mm; P = 0.019). The difference between horizontal BMO diameter minus horizontal gamma zone width decreased (P < 0.001) with longer axial length. Beyond 26.0 mm of axial length, horizontal and vertical BMO diameter increased by 0.21 mm (95% CI: 0.16, 0.27) and 0.12 mm (95% CI: 0.06, 0.18), respectively, for each millimeter of axial elongation. Gamma zone may develop due to an axial elongation-associated BMO enlargement (β: 0.46) and, to a minor degree, a BMO shift in direction to the macula (β: 0.14). A large gamma zone may be protective against myopic macular BM defects.

BackgroundTo examine histomorphometrically the parapapillary region in human eyes.Methodology/Principal FindingsThe histomorphometric study included 65 human globes (axial length:21–37 mm). On anterior-posterior histological sections, we measured the distance Bruch's membrane end (BME)-optic nerve margin (“Gamma zone”), BME-retinal pigment epithelium (RPE) (“Beta zone”), BME-beginning of non-occluded choriocapillaris, and BME-beginning of photoreceptor layer. “Delta zone” was defined as part of gamma zone in which blood vessels of at least 50 µm diameter were not present over a length of >300 µm. Beta zone (mean length:0.35±0.52 mm) was significantly (P = 0.01) larger in the glaucoma group than in the non-glaucomatous group. It was not significantly (P = 0.28) associated with axial length. Beta zone was significantly (P = 0.004) larger than the region with occluded choriocapillaris. Gamma zone (mean length:0.63±1.25 mm) was associated with axial length (P<0.001;r2 = 0.73) with an increase starting at an axial length of 26.5 mm. It was not significantly (P = 0.24) associated with glaucomatous optic neuropathy. Delta zone (present only in eyes with axial length of ≥27 mm) was associated with axial length (P = 0.001) and scleral flange length (P<0.001) but not with glaucoma (P = 0.73).Conclusions/SignificanceParapapillary gamma zone (peripapillary sclera without overlying choroid, Bruch's membrane and deep retinal layers) was related with axial globe elongation and was independent of glaucoma. Delta zone (no blood vessels >50 µm diameter within gamma zone) was present only in highly axially elongated globes and was not related with glaucoma. Beta zone (Bruch's membrane without RPE) was correlated with glaucoma but not with globe elongation. Since the region with occluded choriocapillaris was smaller than beta zone, complete loss of RPE may have occurred before complete choriocapillaris closure.

PurposeTo assess whether macular Bruch´s membrane gets lengthened in axial myopia.MethodsUsing the enhanced depth imaging mode of spectral-domain optical coherence tomography and examining a subgroup of participants of the population-based cross-sectional Beijing Eye Study, we measured the length of Bruch´s membrane (“MacBMLength”) from the fovea to the temporal edge of parapapillary gamma zone, and the distance between the fovea and the temporal optic disc border. Parapapillary gamma zone was defined as the parapapillary region without Bruch´s membrane. We additionally measured ocular biometric parameters and assessed non-ophthalmologic variables.ResultsMeasurements of MacBMLength were performed on 322 individuals. MacBMLength (mean: 3.99±0.33 mm; range: 3.17–4.93 mm) was not significantly associated with any systemic parameter or ocular biometric parameter. Gamma zone width (mean: 0.18±0.30mm; range: 0.00–2.61mm) was associated (multivariate analysis; correlation coefficient r:0.80) with longer axial length (P<0.001; standardized correlation coefficient beta: 0.60; non-standardized correlation coefficient B:0.11; 95%CI: 0.09,0.14) and with longer fovea-optic disc border distance (P<0.001; beta:0.28; B:0.19; 95%CI:0.14,0.25), but not with MacBMLength (P = 0.42). Fovea-temporal disc border distance (mean: 4.16±0.44mm; range: 3.17–5.86mm) was associated (overall correlation coefficient: 0.68) with longer axial length (P<0.001; beta: 0.36; B: 0.10; 95%CI: 0.06, 0.13), after adjusting for flatter anterior chamber depth (P = 0.003; beta:-0.14; B:-0.14; 95%CI: -0.23,-0.05) and wider parapapillary gamma zone (P<0.001; beta:0.42; B:0.62; 95%CI:0.44,0.81).ConclusionsIn contrast to parapapillary gamma zone width and fovea-disc border distance, MacBMLength was not significantly associated with axial length. Axial elongation associated increase in fovea-disc distance may predominantly occur through development or elongation of parapapillary gamma zone, while macular Bruch´s membrane may mostly be independent of axial elongation.

PurposeTo describe nonpathological myopia-related characteristics of the human eye.MethodsBased on histomorphometric and clinical studies, qualitative and quantitative findings associated with myopic axial elongation are presented.ResultsIn axial myopia, the eye changes from a spherical shape to a prolate ellipsoid, photoreceptor, and retinal pigment epithelium cell density and total retinal thickness decrease, most marked in the retroequatorial region, followed by the equator. The choroid and sclera are thin, most markedly at the posterior pole and least markedly at the ora serrata. The sclera undergoes alterations in fibroblast activity, changes in extracellular matrix content, and remodeling. Bruch's membrane (BM) thickness is unrelated to axial length, although the BM volume increases. In moderate myopia, the BM opening shifts, usually toward the fovea, leading to the BM overhanging into the nasal intrapapillary compartment. Subsequently, the BM is absent in the temporal region (such as parapapillary gamma zone), the optic disc takes on a vertically oval shape, the fovea–optic disc distance elongates without macular BM elongation, the angle kappa reduces, and the papillomacular retinal vessels and nerve fibers straighten and stretch. In high myopia, the BM opening and the optic disc enlarge, the lamina cribrosa, the peripapillary scleral flange (such as parapapillary delta zone) and the peripapillary choroidal border tissue lengthen and thin, and a circular gamma and delta zone develop.ConclusionsA thorough characterization of ocular changes in nonpathological myopia are of importance to better understand the mechanisms of myopic axial elongation, pathological structural changes, and psychophysical sequelae of myopia on visual function.

Low-Concentration Atropine for Myopia Progression (LAMP) Study: A Randomized, Double-Blinded, Placebo-Controlled Trial of 0.05%, 0.025%, and 0.01% Atropine Eye Drops in Myopia Control

Myopic axial elongation is associated with various non‐pathological changes. These include a decrease in photoreceptor cell and retinal pigment epithelium (RPE) cell density and retinal layer thickness, mainly in the retro‐equatorial to equatorial regions; choroidal and scleral thinning pronounced at the posterior pole and least marked at the ora serrata; and a shift in Bruch's membrane opening (BMO) occurring in moderately myopic eyes and typically in the temporal/inferior direction. The BMO shift leads to an overhang of Bruch's membrane (BM) into the nasal intrapapillary compartment and BM absence in the temporal region (i.e., parapapillary gamma zone), optic disc ovalization due to shortening of the ophthalmoscopically visible horizontal disc diameter, fovea–optic disc distance elongation, reduction in angle kappa, and straightening/stretching of the papillomacular retinal blood vessels and retinal nerve fibres. Highly myopic eyes additionally show an enlargement of all layers of the optic nerve canal, elongation and thinning of the lamina cribrosa, peripapillary scleral flange (i.e., parapapillary delta zone) and peripapillary choroidal border tissue, and development of circular parapapillary beta, gamma, and delta zone. Pathological features of high myopia include development of macular linear RPE defects (lacquer cracks), which widen to round RPE defects (patchy atrophies) with central BM defects, macular neovascularization, myopic macular retinoschisis, and glaucomatous/glaucoma‐like and non‐glaucomatous optic neuropathy. BM thickness is unrelated to axial length. Including the change in eye shape from a sphere in emmetropia to a prolate (rotational) ellipsoid in myopia, the features may be explained by a primary BM enlargement in the retro‐equatorial/equatorial region leading to axial elongation.

Myopia: Histology, clinical features, and potential implications for the etiology of axial elongation.

To assess prevalence and size of the parapapillary beta zone and gamma zone in a healthy population. Within the population-based Beijing Eye Study, individuals without retinal or optic nerve disease were selected. Using optical coherence tomography (OCT), we measured the parapapillary beta zone (defined by presence of Bruch's membrane and absence of RPE) and gamma zone (region between Bruch's membrane end and optic disc border). The study included 723 individuals (mean age: 59.5 ± 7.6 years; range: 50-90 years). The beta zone was detected in 525 eyes (72.6%; 95% confidence interval [CI]: 69.4, 75.9). A larger maximum width of the beta zone (mean: 253 ± 225 μm) was associated (multivariate analysis; regression coefficient r2: 0.36) with older age (P < 0.001; standardized regression coefficient beta: 0.28), thinner temporal parapapillary choroidal thickness (P < 0.001; beta: -0.21), longer axial length (P < 0.001; beta: 0.14), longer vertical Bruch's membrane opening (BMO) length (P < 0.001; beta: 0.32), shorter horizontal BMO length (P = 0.003; beta: -0.12), and more pronounced vertical optic disc rotation of (P < 0.001; beta: 0.15). The gamma zone was detected in 190 eyes (26.3 ± 1.6%; 95% CI: 23.1, 29.5). A larger maximal width of the gamma zone (mean: 86 ± 187 μm) was (r2: 0.49) associated with longer axial length (P < 0.001; beta: 0.46), thinner central corneal thickness (P < 0.001; beta: 0.10), thinner temporal parapapillary choroidal thickness (P < 0.001; beta: -0.11), longer vertical (P < 0.001; beta: 0.15), and horizontal (P = 0.02; beta: 0.08) BMO length, and more pronounced vertical rotation of optic disc (P < 0.001; beta: 0.32). As measured by OCT in this healthy adult Chinese population, the gamma zone was mainly associated with longer axial length but not with age, while the beta zone was correlated mainly with older age and also with axial length. Both zones were largest in the temporal parapapillary region and smallest in the nasal region.

To investigate the morphological features of parapapillary beta zone and gamma zone and their associated factors in eyes with chronic primary angle-closure glaucoma (CACG). The observational cross-sectional study included 65 CACG eyes and 65 non-myopic control eyes. On enhanced depth imaging of optical coherent tomography images, the area of parapapillary beta zone and gamma zone, and the peripapillary choroidal thickness at 6 sectors were measured. The optic disc ovality index and Bruch's membrane opening (BMO) shape were further calculated. Beta zone was present in 103 (79.2%) eyes and gamma zone in 29 (22.3%) eyes. Compared to control eyes, CACG was associated with larger parapapillary beta zone, female gender, and older age (P < 0.01). No significant difference was observed in axial length and peripapillary choroidal thickness between both groups (P > 0.05). In multivariate analysis, beta zone area was positively associated with older age and higher prevalence of CACG (P < 0.01), while a larger gamma zone area was associated with a smaller disc ovality index and a higher BMO ovality ratio (P < 0.01). The peripapillary choroidal thickness at six sectors was decreased with older age (P < 0.01). In mainly non-myopic subjects with or without CACG, larger parapapillary beta zone was correlated with older age and presence of glaucoma, while a larger parapapillary gamma zone was correlated with disc ovality but not with glaucoma. Parapapillary beta zone and gamma zone may play different roles in physiological and glaucomatous changes around optic nerve head.

The parapapillary gamma zone has been defined as the parapapillary region without Bruch's membrane. We examined which morphologic parameters are associated with the presence and size of the parapapillary gamma zone. Using fundus photographs and spectral-domain optical coherence tomographic images of the optic nerve head in the population-based Beijing Eye Study, we determined parapapillary gamma zone width, macular Bruch's membrane length, optic disc-fovea distance, the angle of horizontal optic disc rotation, the angle of vertical optic disc rotation, and the ratio of the vertical-to-horizontal disc diameter. The study included 2068 individuals with a mean age of 63.0 ± 9.0 years (range, 50-91 years), and mean axial length was 23.2 ± 1.0 mm (range, 18.96-28.87 mm). In multivariate analysis, larger width of parapapillary gamma zone was associated with more marked vertical optic disc rotation (P < 0.001; standardized correlation coefficient β, 0.15; nonstandardized correlation coefficient B, 0.02; 95% confidence interval [CI], 0.02, 0.03), more marked horizontal optic disc rotation (P = 0.02; β, 0.05; B, 0.01; 95% CI, 0.001, 0.01), longer axial length (P = 0.01; β, 0.07; B, 0.02; 95% CI, 0.01, 0.04), longer horizontal optic disc diameter (P = 0.02; β, 0.05; B, 0.06; 95% CI, 0.01, 0.12), longer disc-fovea distance (P < 0.001; β, 0.25; B, 0.22; 95% CI, 0.18, 0.27), higher degree of fundus tessellation (P = 0.03; β, 0.17; B, 0.04; 95% CI, 0.03, 0.0), and thinner subfoveal choroidal thickness (P < 0.001; β, -0.13; B, 0.000; 95% CI, -0.001, 0.000). Parapapillary gamma zone width was not significantly associated with macular Bruch's membrane length (P = 0.72), disc-fovea angle (P = 0.62), age (P = 0.62), or sex (P = 0.46). The parapapillary gamma zone was associated with an axial elongation-induced rotation of the optic disc mainly around the vertical disc axis, leading to a stretching of the temporal peripapillary scleral flange. Because macular Bruch's membrane length was independent of axial elongation, it leaves the temporal parapapillary region with an uncovered Bruch's membrane (i.e., parapapillary gamma zone develops).