Bruch's membrane and Brücke's muscle in the pars plana region.

PURPOSE: To examine Bruch's membrane (BM) in association with the longitudinal part of the ciliary muscle (LPCM) in the pars plana region. METHODS: Using light microscopy, we histomorphometrically assessed BM and the LPCM in the pars plana region. RESULTS: The histomorphometric study included 51 eyes (51 patients; mean age: 60.8 ± 15.0 years; axial length: 26.0 ± 3.3 mm; range: 21.0-36.0 mm). The LPCM (total length: 4.60 ± 1.10 mm) ended 1.15 ± 0.56 mm anterior to the ora serrata. Within the pars plana region, the LPCM (length: 2.58 ± 0.98 mm) had direct contact with BM for 1.95 ± 0.99 mm (71.1 ± 18.4% of the BM undersurface), while a capillary layer was interposed between the BM and the LPCM for 0.70 ± 0.40 mm (29.0 ± 18.4%). In the pars plana region free of LPCM close to the ora serrata, the percentage of BM covered by the capillary layer was higher than in the pars plana region containing the LPCM (63.0 ± 42.1% vs. 29.0 ± 18.4%; p < 0.001). At the LPCM end, BM was in direct contact with a collagenous tissue from the LPCM and was focally thickened as compared to BM with an underlying capillary layer (9.5 ± 5.3 µm vs. 4.3 ± 1.2 µm; p < 0.001). CONCLUSIONS: The direct contact of BM with the LPCM in the pars plana in association with focal BM thickening at the LPCM end suggests an insertion of LPCM on the BM. Taking into account the biomechanical strength of BM, it may imply a functional unit of the LPCM with BM in the process of accommodation with a secondary movement of the posterior BM and tertiary thickening of the subfoveal choroidal space.

Ciliary body size in chronic angle-closure glaucoma.

To examine the size of the ciliary body stroma (CBS) in dependence of the morphology of the anterior chamber angle in enucleated human eyes, we histomorphometrically examined human enucleated eyes. The study included 107 eyes (with a mean axial length of 25.1 ± 2.8 mm (range 21.0-36.0 mm). The anterior chamber angle was open in 68 eyes and it was closed and endothelialized in 39 eyes. The maximal CBS width (541 ± 210 µm versus 59 ± 179 µm; P < 0.001) and the minimal CBS width (214 ± 107 µm versus 17 ± 55 µm; P < 0.001) and maximal ciliary muscle height (593 ± 557 µm versus 293 ± 111 µm; P = 0.001) were significantly smaller in the angle-closure group than in the open-angle group. Maximal CBS width increased with presence of an open anterior chamber angle (beta: 0.82; B: 517; 95% CI 435, 599; P < 0.001) and longer axial length (beta: 0.17; B: 18.2; 95% CI 4.2, 32.2; P = 0.01). Minimal CBS width increased with the presence of an open anterior chamber angle (beta: 0.48; B: 131; 95% CI 80.4, 181; P < 0.001) and a larger maximal ciliary muscle height (beta: 0.33; B: 0.28; 95% CI 0.12, 0.44; P = 0.001). Maximal ciliary muscle height correlated with the maximal CBS height (beta: 0.35; B: 0.53; 95% CI 0.25, 0.81; P < 0.001). The findings suggest that the CBS size is markedly smaller in eyes with a chronically closed endothelialized anterior chamber angle than in eyes with open angles. The tightening of the angle in eyes with angle-closure may prevent the access of aqueous humor not only to the trabecular meshwork but also to the ciliary body and may reduce the uveoscleral or uveovortex outflow pathway.

Choriocapillaris, Photoreceptors, and Inner Retinal Layer in Spatial Relationship to Parapapillary Alpha, Beta, Gamma, and Delta Zones.

Purpose: To examine the spatial relationships between the retinal inner nuclear layer (INL), outer nuclear layer (ONL), retinal pigment epithelium (RPE) layer, Bruch's membrane (BM), and choriocapillaris in the parapapillary region. Methods: Human eyes enucleated due to uveal melanomas or secondary angle-closure glaucoma were histomorphometrically examined. We compared the tissue dimensions between four groups of eyes categorized based on the presence/absence of high myopia and glaucoma. Results: The investigation consisted of 100 globes (axial length: 25.6 ± 3.1 mm; range: 20.0-35.0 mm). In non-highly myopic nonglaucomatous eyes, the INL, ONL, RPE, BM, and choriocapillaris ended approximately at the end of the RPE layer, with no significant (all P ≥ 0.10) difference between the layers in their distance to the RPE-layer end. From non-highly myopic nonglaucomatous eyes to non-highly myopic glaucomatous eyes, highly myopic nonglaucomatous eyes, and eventually highly myopic glaucomatous eyes, the choriocapillaris, INL, and ONL increasingly extended into the beta zone, most marked for the choriocapillaris and least marked for the ONL. A larger extension of the choriocapillaris into the parapapillary beta zone correlated with longer axial length (standardized regression coefficient ß, 0.24; B, 23.0; 95% confidence interval [CI], 1.6-44.5; P = 0.04) and wider parapapillary beta zone (ß, 0.59; B, 0.32; 95% CI, 0.22-0.41; P < 0.001); a larger extension of the INL correlated with longer axial length (ß, 0.34; B, 43.7; 95% CI, 11.6-75.7; P = 0.009), longer gamma zone (ß, 0.52; B, 0.28; 95% CI, 0.15-0.41; P < 0.001), and diagnosis of non-highly myopic glaucoma (ß, 0.28; B, 267; 95% CI, 80.8-454; P = 0.006); and a larger extension of the ONL into parapapillary beta zone correlated with longer axial length (ß, 0.50; B, 32.2; 95% CI, 21.6-42.8; P < 0.001) and wider parapapillary beta zone (ß, 0.28; B, 0.10; 95% CI, 0.04-0.16; P < 0.001). Conclusions: Nonglaucomatous non-highly myopic eyes differ from highly myopic eyes and glaucomatous eyes in the spatial relationship of the parapapillary tissue layers.

Parapapillary drusen of the retinal pigment epithelium.

PURPOSE: To describe the occurrence, morphology and associations of parapapillary drusen of the retinal pigment epithelium (RPE-drusen). METHODS: Using light microscopy, we histomorphometrically examined enucleated human eyes. RESULTS: The study included 83 eyes (axial length: 25.9 ± 3.2 mm; range: 20.0-35.0 mm). Eyes with parapapillary RPE-drusen (n = 29 (35%) eyes) as compared to those without drusen had a significantly shorter axial length (24.0 ± 1.8 mm vs 27.0 ± 3.3 mm; p < 0.001), higher prevalence (27/29 vs 12/54; p < 0.001) and longer width (213 ± 125 µm vs 96 ± 282 µm; p < 0.0001) of parapapillary alpha zone, and thicker BM in parapapillary beta zone (8.4 ± 2.7 µm vs 3.9 ± 2.0 µm; p < 0.001) and alpha zone (6.6 ± 3.9 µm vs 4.4 ± 1.5 µm; p = 0.02). Prevalence of parapapillary RPE-drusen was 27 (69%) out of 39 eyes with alpha zone. Beneath the RPE-drusen and in total alpha zone, choriocapillaris was open, while it was closed in the central part of parapapillary beta zone. BM thickness was thicker (p = 0.001) in alpha zone than beta zone, where it was thicker (p < 0.001) than in the region outside of alpha/beta zone. BM thickness outside of alpha/beta zone was not correlated with prevalence of parapapillary RPE-drusen (p = 0.47) or axial length (p = 0.31). RPE cell density was higher in alpha zone than in the region adjacent to alpha zone (22.7 ± 7.3 cells/240 µm vs 18.3 ± 4.1 cells/240 µm; p < 0.001). In the parapapillary RPE-drusen, RPE cells were connected with a PAS-positive basal membrane. CONCLUSIONS: Parapapillary RPE-drusen as fibrous pseudo-metaplasia of the RPE were associated with shorter axial length, higher prevalence and larger size of alpha zone, and thicker BM in alpha zone and beta zone. The RPE-drusen may be helpful to differentiate glaucomatous parapapillary beta zone from myopic beta zone.

Myopic Versus Glaucomatous Parapapillary Beta Zone in Myopic Eyes Versus Eyes With Secondary Angle-Closure Glaucoma.

Purpose: To search for histologic differences in the beta zone between myopic eyes versus eyes with secondary angle-closure glaucoma. Methods: The histomorphometric study consisted of human eyes enucleated due to uveal melanomas or secondary angle-closure glaucoma. Results: The study included 100 eyes (age: 62.1 ± 15.1 years; axial length: 25.6 ± 3.1 mm; range: 20.0-35.0 mm). In non-highly myopic glaucomatous eyes compared with non-highly myopic nonglaucomatous eyes, the parapapillary alpha zone was longer (223 ± 168 µm vs. 125 ± 128 µm; P = 0.03), beta zone prevalence (15/20 vs. 6/41; P < 0.001) and length (277 ± 245 µm vs. 44 ± 150 µm; P = 0.001) were higher, and RPE cell density in the alpha zone and alpha zone border was lower (all P < 0.05). In highly myopic nonglaucomatous eyes compared with non-highly myopic glaucomatous eyes, parapapillary RPE drusen prevalence (2/19 vs. 10/10; P = 0.01) and alpha zone prevalence (2/19 vs. 16/20; P < 0.001) and length (23 ± 68 µm vs. 223 ± 168 µm; P < 0.001) were lower. In non-highly myopic glaucomatous eyes, Bruch's membrane (BM) thickness decreased (P < 0.001) from the beta zone (6.0 ± 3.1 µm) to the alpha zone (5.1 ± 4.3 µm) and peripheral to it (3.0 ± 0.9 µm). In highly myopic nonglaucomatous eyes, BM thickness did not differ (P > 0.10) between all three regions. In the total study population, RPE cell density in the alpha zone (24.5 ± 9.3 cells/240 µm) was higher than at the alpha zone border (19.2 ± 4.8 cells/240 µm; P < 0.001) or peripheral to it (19.0 ± 3.6 cells/240 µm; P < 0.001). Conclusions: The glaucomatous beta zone in eyes with chronic angle-closure glaucoma (with the alpha zone, parapapillary RPE drusen, thickened BM, and higher RPE cell count in the adjacent alpha zone) differs histologically from the myopic beta zone (characterized by the absence of the alpha zone and parapapillary RPE drusen, unremarkable BM thickness, and unremarkable parapapillary RPE). The differences suggest different etiologies of the glaucomatous versus myopic beta zone.

Histopathology of myopic cobblestones.

PURPOSE: To search for the histological correlate of peripheral 'cobblestones' in highly myopic eyes. METHODS: The histomorphometric investigation included histologic sections of enucleated eyes of Caucasian patients. Using light microscopy, we measured the thickness of the retina, Bruch's membrane (BM) and choriocapillaris. RESULTS: The study included 50 eyes (mean age:60.6 ± 18.7 years;axial length:26.5 ± 3.8 mm), with cobblestone regions detected in 7 eyes. BM thickness and choriocapillaris thickness in the cobblestone region were thinner (1.1 ± 0.2 µm versus 2.4 ± 0.8 µm; p < 0.001 and 1.6 ± 0.5 µm versus 2.6 ± 1.9 µm; p = 0.02, respectively), and just outside of the cobblestone region they were thicker (3.3 ± 0.6 µm versus 2.4 ± 0.8 µm; p = 0.005 and 5.7 ± 1.6 µm versus 2.6 ± 1.9 µm; p = 0.002, respectively) than in corresponding regions of eyes without cobblestones. Within the group of eyes with cobblestones, BM thickness (1.1 ± 0.2 mm versus 3.3 ± 0.6 mm; p < 0.001), choriocapillaris thickness (1.6 ± 0.5 mm versus 5.7 ± 1.6 mm; p < 0.001) and choriocapillaris density (48±15 µm/300 µm versus 159 ± 66 µm/300 µm;PP=0.002) were significantly lower in the cobblestone region than just outside of the cobblestone region. The cobblestone regions were characterized by firm adhesion of disorganized retina with thinned BM, few retinal pigment epithelium (RPE) islands within cobblestone regions, and absence of regional scleral or overall choroidal thinning. BM was mono-layered within, and double-layered outside of cobblestone regions, with the inner layer missing within the cobblestone region (except for the RPE islands). CONCLUSIONS: Peripheral cobblestone regions in highly myopic eyes are characterized by marked BM thinning with absence of an inner BM layer, almost complete RPE absence, choriocapillaris thinning and firm connection of a disorganized retina to BM. These findings may help elucidating the process of axial elongation in myopic eyes.

Histology of neovascular myopic macular degeneration.

To assess the histological correlate of neovascular or exudative myopic macular degeneration (nMMD) in highly myopic human eyes, we examined histomorphometrically histologic sections of enucleated eyes of Caucasian patients. The study included 284 eyes (age: 61.9 ± 13.7 years; range: 24-89 years; axial length: 25.5 ± 3.1 mm; range: 20-37 mm). An nMMD was detected in 5 eyes (axial length: 29.6 ± 2.6 mm; range: 26.0-31.0 mm). All these eyes showed within or close to the nMMD a macular Bruch's membrane (BM) defect, fibrous tissue with erythrocyte-filled blood vessels, and proliferations of irregularly pigmented and irregularly piled-up retinal pigment epithelium (RPE) cells each of which was connected with a curled-up, PAS (Periodic-Acid-Shiff)-positive membrane. The nMMD lesions were covered by proliferated RPE cells. RPE cells were not detected within the retina. In binary regression analysis, a higher nMMD prevalence was associated with a higher prevalence of macular BM defects (odds ratio: > 1000; P < 0.001), while the association with axial length was not significant (P = 0.43) in that model. After adjustment for the presence of macular BM defects, the nMMD prevalence was not associated with BM thickness (measured at the posterior pole, equator-posterior pole midpoint, equator and shortly posterior to the ora serrata) (P = 0.10; P = 0.87; P = 0.40; and P = 0.36, respectively), RPE cell layer thickness (P = 0.83; P = 0.79; P = 0.31; P = 0.38, resp.), RPE cell density (P = 0.56; P = 0.91; P = 0.47; P = 0.87, resp.), choriocapillaris thickness (P = 0.47; P = 0.93; P = 0.41; P = 0.75, resp.), and choriocapillaris density (P = 0.99; P = 0.94; P = 0.17; P = 0.97, resp.). The results suggest that nMMD is characterized by a fibrous pseudo-metaplasia of the RPE and is strongly associated with macular BM defects, without other detected histomorphometric differences in thickness or density of the RPE, BM, and choriocapillaris.

Optic nerve head morphology in young patients after antiglaucomatous filtering surgery.

PURPOSE: To compare the optic nerve head appearance in glaucomatous eyes before and after marked reduction of intraocular pressure (IOP). METHODS: The hospital-based observational case-series study included selected glaucoma patients for whom optic disc photographs taken before and 1 week to 5 months after surgical reduction of IOP were morphometrically examined. RESULTS: The study included 23 eyes of 16 patients (mean age: 28.7 ± 6.0 years). Mean preoperative IOP was 31.6 ± 7.7 mmHg (22-52 mmHg), and mean IOP drop was 21.5 ± 8.4 mmHg (11-45 mmHg). The horizontal disc diameter decreased significantly (p < 0.001) after surgery, while the vertical disc diameter did not change markedly (p = 0.54). The width of the neuroretinal rim increased significantly in all disc quadrants (all p-values ≤ 0.01), optic cup depth decreased (p < 0.001), and reflectivity of the inner retinal surface increased significantly (p < 0.001). Some eyes showed a pronounced reduction in beta zone of parapapillary atrophy parallel to an increase in horizontal disc diameter, and some eyes showed an enlargement of beta zone parallel to a reduction in horizontal disc diameter. CONCLUSIONS: After marked reduction of high IOP, some eyes of young adult patients with glaucoma can show a horizontal shrinkage of the optic nerve head, in addition to a partial restoration of the neuroretinal rim and a flattening of the optic cup. In addition, beta zone of parapapillary atrophy can decrease or increase, complementarily to changes in the horizontal disc diameter. These findings may be of interest for the biomechanics of the optic nerve head and the precision of imaging techniques.

Parapapillary atrophy: histological gamma zone and delta zone.

BACKGROUND: To examine histomorphometrically the parapapillary region in human eyes. METHODOLOGY/PRINCIPAL FINDINGS: The 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;r(2) = 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/SIGNIFICANCE: Parapapillary 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.

Histology of the parapapillary region in high myopia.

PURPOSE: To examine histomorphometrically the parapapillary region in highly myopic eyes. DESIGN: Retrospective laboratory investigation. METHODS: We examined a highly myopic glaucomatous group (36 human globes; axial length >26.5 mm) and a non-highly myopic group (28 globes with secondary angle-closure glaucoma; 17 eyes with malignant choroidal melanoma). Using light microscopy, pupil-optic nerve sections were assessed. RESULTS: The length of the scleral flange (sclera between optic nerve border and optic nerve dura mater) increased with axial length (P < .001; correlation coefficient r = 0.70) and decreased with its thickness (P < .001; r = 0.75). In all highly myopic eyes (n = 15) with a distance of >0.5 mm between optic nerve border and beginning of Bruch membrane, the parapapillary region consisted of an elongated parapapillary scleral flange associated with a scleral flange thinning and a retrobulbar cerebrospinal fluid space extended into the retroparapapillary region. The parapapillary retina was composed of retinal nerve fiber layer (or its remnants) only, without elements of any other retinal layer, without underlying Bruch membrane or choroid. These histologic features were not detected in any of the non-highly myopic eyes. CONCLUSIONS: Since parapapillary scleral thickness influences the lamina cribrosa biomechanics, the findings may partially explain the increased glaucoma susceptibility in highly myopic eyes. The implications of an absence of Bruch membrane and choroid in the highly myopic parapapillary region, and the implications of the retrobulbar parapapillary extension of the cerebrospinal spinal fluid space for the pathophysiology of the optic nerve head, have to be elucidated.

Histomorphometry of the circular peripapillary arterial ring of Zinn-Haller in normal eyes and eyes with secondary angle-closure glaucoma.

PURPOSE: To examine the location and size of the peripapillary arterial circle of Zinn-Haller (PACZH) and its associations with other eye measures in normal eyes and eyes with secondary angle-closure glaucoma. METHODS: The study included 29 human globes enucleated because of malignant choroidal melanoma (n = 19) (control group) or because of secondary angle-closure glaucoma (n=10). Anterior-posterior histological sections were morphometrically evaluated. RESULTS: The PACZH was present in all eyes. The glaucoma group and the control group did not vary significantly in the distance from the PACZH to Bruch's membrane (297 ± 67 versus 270 ± 67 µm; p = 0.29), optic disc border (281 ± 103 versus 391 ± 170 µm; p=0.07), optic disc centre (1059 ± 191 versus 978 ± 205µm; p = 0.30) and retrobulbar cerebrospinal fluid space (173 ± 58 versus 172 ± 81 µm; p = 0.97) nor in the minimal PACZH diameter (39± 18 versus 36 ± 18 µm; p = 0.74) and maximal PACZH diameter (78 ±37 versus 65 ± 25 µm; p = 0.36). The PACZH location, measured as distance from Bruch's membrane, disc border, disc centre and cerebrospinal fluid space, was not significantly associated with axial length (p > 0.39), horizontal globe diameter (p > 0.17) and vertical globe diameter (p > 0.22). Both diameters were statistically independent of axial length (p = 0.72 and p = 0.58, respectively), horizontal globe diameter (p = 0.60 and p = 0.41, respectively) and vertical globe diameter (p = 0.64 and p = 0.52, respectively). All parameters were statistically independent of age (p > 0.10) and gender (p > 0.10). CONCLUSIONS: The PACZH was present in all human eyes examined and did not vary significantly in location and diameter between eyes with secondary angle-closure glaucoma and nonglaucomatous eyes, nor between myopic versus hyperopic eyes.