Association between axial length and horizontal and vertical globe diameters.

PURPOSE: To assess relationships between axial length and the horizontal and vertical globe diameters. MATERIAL AND METHODS: The study consisted of enucleated human eyes. The horizontal, vertical, and sagittal diameters were measured. RESULTS: The study included 135 globes removed because of malignant uveal melanoma (111 globes) or end-stage painful glaucoma (n = 24 eyes). Mean axial, horizontal, and vertical diameters were 24.6 ± 2.6 mm (range: 20-35 mm), 23.7 ± 1.4 mm (range: 21-29 mm) and 23.7 ± 1.4 mm (range: 20-29 mm) respectively. The horizontal diameter and vertical diameter did not differ significantly (P = 0.92), while both were significantly (P < 0.001) shorter than the axial diameter. The horizontal diameter was significantly and linearly correlated with the vertical globe diameter (P < 0.001; regression line: vertical globe diameter = 0.84 × horizontal globe diameter + 3.69). The axial diameter was significantly (P < 0.001) associated with the horizontal diameter and vertical diameters in a bipartite manner. In eyes with an axial length ≤24 mm, horizontal and vertical diameters increased by 0.44 and 0.51 mm, respectively, for each mm increase in axial diameter, while in eyes with an axial length >24 mm, the horizontal and vertical globe diameter increased by a lower amount of 0.19 and 0.21 mm, respectively, for each mm increase in axial diameter. CONCLUSIONS: Myopic enlargement of the globe beyond an axial length of 24 mm takes place predominantly in the sagittal axis, leading to a change in the globe form from a sphere to an elongated form. It fits with the notion that myopic elongation may occur by an elongation of the eye walls in regions close to the globe's equator.

Bilateral Orbital IgG4-Related Disease with Systemic and Corneal Involvement Showing an Excellent Response to Steroid and Rituximab Therapy: Report of a Case with 11 Years Follow-Up.

IgG4-related disease is a newly recognized fibro-inflammatory condition. The purpose of this report is to present a patient with 11 years of follow-up, who revealed characteristic features of IgG4-related disease with systemic, orbital and corneal involvement and showed a favorable response to steroids and rituximab treatment.

Prognostic significance of tumor-associated lymphangiogenesis in malignant melanomas of the conjunctiva.

PURPOSE: To evaluate whether tumor-associated lymphangiogenesis contributes to prognosis of conjunctival malignant melanomas and to study its association with other tumor characteristics. DESIGN: Nonrandomized, retrospective case series. PARTICIPANTS: A total of 109 consecutive patients with primary conjunctival malignant melanoma. METHODS: Proliferating lymphatic vessels were identified immunohistochemically using lymphatic vascular endothelial hyaluronan receptor-1 and podoplanin as specific lymphatic endothelial markers and Ki-67 as proliferation marker. Baseline tumor characteristics included tumor location, tumor thickness, tumor diameter, tumor origin, and tumor growth pattern. Kaplan-Meier and Cox regression analyses of the risk of local recurrence, lymphatic spread, distant metastasis, and melanoma-related death were performed. MAIN OUTCOME MEASURES: Intratumoral lymphatic vascular density and its association with tumor characteristics and recurrence-free, lymphatic spread-free, distant metastasis-free, and melanoma-specific survival. RESULTS: Intratumoral and peritumoral proliferating lymphatic vessels could be detected in all of the 109 conjunctival melanoma samples. High intratumoral lymphatic density was significantly associated with palpebral tumor location (P<0.001), greater tumor thickness (P<0.001), larger tumor diameter (P = 0.001), tumor origin de novo (P = 0.002), and nodular tumor growth pattern (P = 0.037). Patients with high intratumoral lymphatic density revealed significantly lower recurrence-free, lymphatic spread-free, distant metastasis-free, and melanoma-specific survival rates (P<0.001 for all). By multivariate Cox regression, factors predictive of local recurrence included palpebral tumor location (hazard ratio [HR] 2.66, P = 0.014), large tumor diameter (HR 5.48, P<0.001), and high intratumoral lymphatic density (HR 2.48, P = 0.043); factors predictive of lymphatic spread included palpebral tumor location (HR 4.13, P = 0.009), high tumor thickness (HR 12.17, P<0.001), and high intratumoral lymphatic density (HR 6.79, P = 0.019); factors predictive of distant metastasis included palpebral tumor location (HR 7.63, P<0.001), high tumor thickness (HR 8.60, P<0.001), large tumor diameter (HR 0.30, P = 0.029), and high intratumoral lymphatic density (HR 8.90, P = 0.047); and factors predictive of melanoma-related death included palpebral tumor location (HR 7.74, P<0.001), high tumor thickness (HR 10.88, P<0.001), large tumor diameter (HR 0.28, P = 0.018), and, with borderline significance, high intratumoral lymphatic density (HR 8.46, P = 0.052). CONCLUSIONS: Tumor-associated lymphangiogenesis seems to be associated with an increased risk of local recurrence, lymphatic spread, distant metastasis, and melanoma-related death in patients with conjunctival malignant melanomas. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Pathogenesis of involutional ectropion and entropion: the involvement of matrix metalloproteinases in elastic fiber degradation.

PURPOSE: To determine the elastic fiber content and ultrastructure as well as the expression of elastin-degrading enzymes in biopsy specimens from patients with involutional ectropion and entropion. MATERIALS AND METHODS: Twenty consecutive patients with involutional ectropion (group 1) and twenty consecutive patients with entropion (group 2) were matched with twenty control patients (basal cell carcinoma) regarding age and gender. Full-thickness eyelid resections performed in study and control patients were examined by light and transmission electron microscopy, computer-assisted measurements, and immunohistochemistry using antibodies against matrix metalloproteinase (MMP)-2, MMP- 7, and MMP-9. The Kruskal-Wallis test and the Pearson chi-square test were performed. RESULTS: Histopathologic analysis of the surgical specimens from patients with involutional ectropion and entropion showed a significant loss of elastic fibers in the eyelid skin, the pretarsal orbicularis oculi muscle, the perimeibomian tarsal stroma, and the intermeibomian tarsal stroma (P < 0.001). Residual elastic fibers revealed an abnormal ultrastructure. Immunohistochemistry demonstrated a significant overexpression of MMP- 2, MMP-7, and MMP-9 in the eyelid skin, the pretarsal orbicularis oculi muscle, the perimeibomian tarsal stroma, the intermeibomian tarsal stroma, and the conjunctiva in groups 1 and 2 compared to controls (P < 0.001). CONCLUSIONS: The present findings indicate that upregulation of elastolytic enzymes contributes to elastic fibre degradation in patients with involutional ectropion and entropion.

Choriocapillaris thickness and density in axially elongated eyes.

PURPOSE: Axial myopia is characterized by a thinning of the choroid. We examined whether the myopic choroidal thinning also includes a thinning of the choriocapillaris. METHODS: Using light microscopy, we measured thickness and density of the choriocapillaris at the posterior pole, posterior pole-equator midpoint (PPEMP), equator and close to the ora serrata on histological sections of 58 enucleated human globes (mean age: 62.4 ± 17.8 years; range: 24-88 years; mean axial length: 27.8 ± 4.0 mm; range: 22.0-37.0 mm). RESULTS: Choriocapillaris thickness decreased (p < 0.001) from the posterior pole (median: 3.9 µm; interquartile range (IQR): 3.3-6.0) to the equator (median: 2.7 µm; IQR: 1.5, 4.2). It was not significantly associated with axial length, neither at the posterior pole (p = 0.25), the PPEMP (p = 0.81), equator (p = 0.80) or ora serrata (p = 0.50). Mean choriocapillaris density decreased from the posterior pole to the equator (198 µm/300 µm; IQR: 152/300, 246/300 versus 156 µm/300 µm; IQR: 72/300, 216/300; p < 0.001). Choriocapillaris density was not significantly associated with axial length (posterior pole: p = 0.07; PPEMP: p = 0.33; equator: p = 0.22; ora serrata: p = 0.36). CONCLUSIONS: The choriocapillaris thickness and density, decreasing from the posterior pole to the fundus periphery, were not significantly associated with axial length. These findings may be of interest for the understanding of high myopia and pathologic myopia.

Tumor-associated lymphangiogenesis in the development of conjunctival squamous cell carcinoma.

PURPOSE: To analyze whether tumor-associated lymphangiogenesis accompanies the development from premalignant conjunctival intraepithelial neoplasia (CIN) into invasive squamous cell carcinoma (SCC) of the conjunctiva and to study its association with prognosis and other tumor characteristics. DESIGN: Case-controlled, matched-pair cohort study. PARTICIPANTS: Twenty patients with invasive SCC were closely matched with 20 patients with high-grade CIN and 20 patients with low-grade CIN regarding tumor size, tumor location, tumor extension, and patients' age. METHODS: Proliferating lymphatic vessels were identified using lymphatic vascular endothelial hyaluronan receptor-1 and podoplanin as specific lymphatic endothelial markers and Ki-67 as proliferation marker. Baseline tumor characteristics included tumor size, tumor-to-limbus distance, tumor-to-fornix distance, 2009 TNM classification, tumor cell type, mitotic rate, and Ki-67 proliferation index. Kaplan-Meier and Cox regression analyses of recurrence-free survival were performed. MAIN OUTCOME MEASURES: Lymphatic vascular density (LVD) and relative lymphatic vascular area (RLVA) of proliferating lymphatic vessels within the tumor mass (intratumoral) and within an area < or = 500 microm from the tumor border (peritumoral), and its association with tumor characteristics and recurrence-free survival. RESULTS: Intratumoral and peritumoral proliferating lymphatic vessels could be detected in all of the 60 conjunctival tumor samples. Invasive SCC revealed significantly higher values of intratumoral and peritumoral LVD and RLVA of proliferating lymphatics than high-grade or low-grade CIN (P < or = 0.001). Higher intratumoral lymphatic densities were significantly associated with larger tumor size (P=0.001), lower tumor-to-limbus distance (P=0.002), lower tumor-to-fornix distance (P=0.003), and higher TNM categories (P<0.001). Recurrence-free survival rates decreased significantly with higher intratumoral lymphatic densities (P<0.001). By multivariate Cox regression, large tumor size (hazard ratio 1.68, P=0.002) and high intratumoral lymphatic density (hazard ratio 1.10, P=0.046) were significant prognostic predictors of local recurrence. CONCLUSIONS: Development of conjunctival SCC from premalignant lesions is accompanied by the outgrowth of new conjunctival lymphatic vessels. This active tumor-associated lymphangiogenesis seems to be associated with an increased risk of local recurrence in patients with CIN and conjunctival invasive SCC. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Intraocular tumor-associated lymphangiogenesis a novel prognostic factor for ciliary body melanomas with extraocular extension?

PURPOSE: To evaluate whether intraocular tumor-associated lymphangiogenesis contributes to prognosis of ciliary body melanomas with extraocular extension and to study its association with other tumor characteristics. DESIGN: Nonrandomized, retrospective case series. PARTICIPANTS: Twenty consecutive patients enucleated for a malignant melanoma of the ciliary body with extraocular extension. METHODS: Lymphatic vessels were identified using lymphatic vascular endothelial-specific hyaluronic acid receptor-1 (LYVE-1) and podoplanin as specific immunohistochemical markers for lymphatic vascular endothelium. Baseline tumor characteristics included intra- and extraocular tumor size, 2009 tumor, node, metastasis (TNM) classification, route of extraocular spread, tumor cell type, mitotic rate, Ki-67 proliferation-index, microvascular patterns and density, tumor-infiltrating lymphocytes and macrophages, and expression of human leukocyte antigen (HLA) class I and insulin-like growth factor-1 receptor. Kaplan-Meier and Cox regression analyses of melanoma-specific survival were performed. MAIN OUTCOME MEASURES: Prevalence of intraocular LYVE-1(+)/podoplanin(+) lymphatic vessels and association with intraocular tumor characteristics and metastasis-free survival. RESULTS: Intraocular LYVE-1(+) and podoplanin(+) lymphatic vessels could be detected in 12 (60%) of 20 ciliary body melanomas with extraocular extension. Presence of intraocular LYVE-1(+)/podoplanin(+) lymphatic vessels was significantly associated with larger intra- (P = 0.002) and extraocular tumor size (P<0.001), higher TNM categories (P = 0.004), epithelioid cellularity (P = 0.016), higher mitotic rate (P = 0.003), higher Ki-67 proliferation-index (P = 0.049), microvascular networks (P = 0.005), higher microvascular density (P = 0.003), more tumor-infiltrating macrophages (P = 0.002), higher expression of HLA class I (P = 0.046), and insulin-like growth factor-1 receptor (P = 0.033), but not significantly with route of extraocular spread (P = 0.803), and tumor-infiltrating lymphocytes (P = 0.069). Melanoma-specific mortality rates increased significantly with the presence of intraocular LYVE-1(+)/podoplanin(+) lymphatic vessels (P = 0.008). By multivariate Cox regression, tumor size (hazard ratio, 14.40; P = 0.002), and presence of intraocular lymphatic vessels (hazard ratio, 8.09; P = 0.04) were strong prognostic predictors of mortality. CONCLUSIONS: Intraocular peritumoral lymphangiogenesis seems to be associated with an increased mortality risk in patients with ciliary body melanomas and extraocular extension. This association may be primarily because of an association of intraocular lymphangiogenesis with greater tumor size and increased malignancy.

Tumors of the lacrimal drainage system.

Tumors of the lacrimal drainage system are rare, but potentially life-threatening. They comprise a large and variable spectrum of entities grouped into three major categories of primary epithelial, primary nonepithelial and inflammatory lesions. The most common primary epithelial tumors include papilloma, squamous cell carcinoma and transitional cell carcinoma, the most frequent primary nonepithelial tumors fibrous histiocytoma, malignant lymphoma and malignant melanoma, and the most common inflammatory lesions sarcoidosis, Wegener granulomatosis and pyogenic granuloma. This review outlines the incidence, types, management and prognosis of tumors affecting the lacrimal drainage system.

Peripapillary border tissue of the choroid and peripapillary scleral flange in human eyes.

PURPOSE: To assess dimensions and associations of the peripapillary border tissue of the choroid (PBT-C) and peripapillary scleral flange (PBT-S). METHODS: The histomorphometric investigation included histological sections of enucleated eyes of Caucasian patients. Using light microscopy, the PBT dimensions were measured. RESULTS: The study included 85 eyes (85 patients) with an age of 62.0 years (14.1 years) (mean (SD)) (range:37-87 years) and mean axial length of 26.7 mm (3.5 mm) (range:21.0-37.0 mm). Thicker PBT-C thickness (mean: 68.8 µm (35.7 µm)) was associated with shorter axial length (p < 0.001; standardized regression coefficient beta: -0.50), and longer PBT-C length (mean: 531 µm (802 µm)) was correlated with longer axial length (p < 0.001;beta:0.66). PBT-C cross-sectional area (mean 17 050 µm2 (10 420 µm2 )) was not significantly associated with axial length (p = 0.37). Decreasing with longer axial length (p < 0.001;beta:0.64), the angle between PBT-C and Bruch's membrane was approximately 90° in non-highly myopic eyes without overhanging Bruch's membrane (BM), it ranged between 100° and 180° in eyes with BM overhanging into the intrapapillary region, and it was close to 0° in eyes with parapapillary gamma zone. Thicker thickness of PBT-S (mean:83 µm (21 µm)) was correlated with presence of glaucoma (p = 0.02). Optic nerve pia mater thickness (mean:109 µm (44 µm)) increased with glaucoma presence (p = 0.046;beta:0.31) but not with axial length (p = 0.34). CONCLUSIONS: Peripapillary border tissue of the choroid (PBT-C) and PBT-S as continuation of the optic nerve pia mater are distinct structures, with PBT-C remodelling during myopic axial elongation and PBT-S being mostly independent of axial elongation. PBT-C and PBT-S may be of importance for the optic nerve head biomechanics and PBT-C for separation of the choroidal space from the intrapapillary compartment.

Retinal Pigment Epithelium Cell Density and Bruch's Membrane Thickness in Secondary versus Primary High Myopia and Emmetropia.

To assess differences between secondary high myopia (SHM) due to congenital glaucoma and primary high myopia (PHM) and non-highly myopic eyes (NHM) in the relationships between axial length and Bruch's membrane (BM) thickness and retinal pigment epithelium (RPE) density. The histomorphometric study included human globes enucleated for reasons such as malignant uveal melanoma, end-stage painful secondary angle-closure glaucoma and congenital glaucoma. BM thickness and RPE cell density were measured upon light microscopy. The investigation included 122 eyes (mean axial length: 26.7 ± 3.7 mm; range: 20.0-37.0 mm): 7 eyes with SHM (axial length: 33.7 ± 2.1 mm; range: 31.0-37.0 mm), 56 eyes with PHM (mean axial length: 29.1 ± 2.4 mm; range: 26.0-36.0 mm) and 59 eyes in the NHM-group (axial length: 23.5 ± 1.3 mm; range: 20.0-25.5 mm). In the SHM group, longer axial length was associated with lower RPE cell density at the posterior pole (standardized regression coefficient beta: 0.92; non- standardized regression coefficient B: -2.76; 95% confidence interval (CI): -4.41, -1.10;P = 0.01), at the midpoint posterior pole/equator (beta: -0.87; B: -3.60; 95% CI: -6.48, -0.73;P = 0.03), and at the equator (beta: -0.88; B: -0.95; 95% CI: -1.68, -0.23; P = 0.02), but not at the ora serrata (P = 0.88). In the PHM-group and NHM group, RPE cell density at the posterior pole (P = 0.08) and ora serrata (P = 0.88) was statistically independent of axial length, while at the midpoint posterior pole/equator (P = 0.01) and equator (P < 0.001), RPE cell density decreased with longer axis. BM thickness in the SHM group decreased with longer axial length at the posterior pole (beta: -0.93;B: -0.29; 95% CI: -0.39, -0.14; P = 0.003), midpoint posterior pole/equator (beta: -0.79; B: -0.22; 95% CI: -0.42, -0.02; P = 0.035) and equator (beta: -0.84; B: -0.21; 95% CI: -0.37, -0.06; P = 0.017), while in the PHM-group and NHM-group, BM thickness at any ocular region was not statistically significantly correlated with axial length (all P > 0.05). In the SHM-group, but not in the PHM-group or NHM-group (P = 0.98), lower BM thickness was associated with lower RPE cell density (beta: 0.93; B: 0.09; 95% CI: 0.04, 0.14; P = 0.007), while in the eyes without congenital glaucoma the relationship was not statistically significant. In SHM in contrast to PHM, BM thickness and RPE cell density decrease in a parallel manner with longer axial length. The findings fit with the notion of BM being a primary driver in the process of axial elongation in PHM as compared to SHM.

Histology of myopic posterior scleral staphylomas.

PURPOSE: Since histomorphometric descriptions of posterior scleral staphylomas, although forming a major part of myopic maculopathy, have been scarce so far, we histomorphometrically examined scleral staphylomas in enucleated human eyes. METHODS: Using light microscopy, we histomorphometrically examined sagittal histological sections of human globes enucleated due to malignant choroidal melanomas or secondary angle-closure glaucoma. RESULTS: Out of 246 globes included into the study, posterior scleral staphylomas were detected in 10 eyes (mean length: 31.4 ± 3.0 mm; range: 28.0-37.0 mm). In the staphylomatous region in the study group as compared with the corresponding region of a control group adjusted for age and axial length, scleral thickness was significantly lower (109 ± 25 µm versus 319 ± 161 µm; p = 0.001). The study group in the staphylomatous region as compared to the highly myopic control group in the corresponding region did not differ significantly in retinal pigment epithelium (RPE) cell density (19.6 ± 4.9 cells/300 µm versus 21.1 ± 5.7 cells/300 µm; p = 0.84) and RPE height (8.2 ± 2.8 µm versus 6.1 ± 2.5 µm; p = 0.13), Bruch's membrane (BM) thickness (3.5 ± 1.3 µm versus 4.2 ± 2.3 µm; p = 0.40) and choriocapillaris thickness (5.3 ± 2.8 µm versus 4.4 ± 2.8 µm; p = 0.49) and density (164 ± 99 µm versus 226 ± 38 µm; p = 0.13). All staphylomatous regions showed a localized BM defect. CONCLUSIONS: Marked scleral thinning and spatially correlated BM defects histologically characterized myopic scleral staphylomas, while thickness and density of the choriocapillaris and RPE and BM thickness did not differ significantly between staphylomatous versus non-staphylomatous eyes in the respective regions. These findings support the notion that a locally reduced scleral resistance against a backward pushing BM led to a local scleral outpouching. The outpouching-associated increase in curvature length may stretch BM with the sequel of a localized BM rupture.

A clinicopathologic study of nasal mucosa in 350 patients with external dacryocystorhinostomy.

PURPOSE: To analyze the frequency, pattern, and extent of chronic inflammation and scarring in nasal mucosa specimens obtained during external dacryocystorhinostomy (DCR), and to correlate these findings with clinical data. METHODS: We reviewed the clinical and histopathologic data of 350 consecutive patients without clinical evidence of rhinological diseases who underwent primary DCR for acquired dacryostenosis. RESULTS: The mean age of the patients (238 females and 112 males) at the time of surgery was 57.4 years (range 34-95 years). Of the 350 patients, 189 (54%) had clinical evidence of acute dacryocystitis previously. Acute dacryocystitis was present in 55 patients (16%) less than one month prior to surgery, in 86 patients (25%) one to six months prior to surgery, and in 48 patients (14%) more than six months prior to surgery. The mean duration of preoperative symptoms (e.g., epiphora, purulent discharge) was 30.2 months (range 1-220 months). The postoperative success rate was 92% (mean follow-up 40.3 months, range 12-93 months). Histopathologically, the presence of chronic inflammation was noted more frequently (p < 0.001, Kruskal-Wallis test), with a shorter time interval between surgery and last dacryocystitis. The presence of subepithelial scarring was detectable more often (p < 0.001, Kruskal-Wallis test), with a longer time interval between surgery and last episode of dacryocystitis. Postoperative success was more common in patients with a shorter duration of preoperative symptoms (p = 0.005, Mann-Whitney test) and with a shorter time interval between surgery and last dacryocystitis (p < 0.001, Student's t-test). CONCLUSION: The histopathologic presence of subepithelial scarring and shrinkage in nasal mucosa biopsy specimens was associated with longer time intervals between dacryocystitis and surgery as well as with less favorable postoperative outcomes. The results of the present study suggest that patients should undergo rather early surgery following the regression of acute inflammation.

Reactive uveitis, retinal vasculitis and scleritis as ocular end-stage of Acanthamoeba keratitis: a histological study.

We analysed histologically two Acanthamoeba keratitis (AK) eyes with anterior and posterior segment inflammation and blindness. Two enucleated eyes of 2 patients (age 45 and 51y) with AK (PCR of epithelial abrasion positive) were analysed. Histological analysis was performed using hematoxylin-eosin, periodic acid-Schiff and Gömöri-methenamine silver staining. We could not observe Acanthamoeba trophozoites or cysts neither in the cornea nor in other ocular tissues. Meanwhile, we found uveitis, retinal vasculitis and scleritis in these eyes, due to the long-standing, recalcitrant AK. So in this stage of AK, systemic immune suppression may be necessary for a longer time period.

Borrelia-associated crystalline keratopathy with intracorneal detection of Borrelia garinii by electron microscopy and polymerase chain reaction.

PURPOSE: First report of a patient with Borrelia-associated crystalline keratopathy with intracorneal evidence of Borrelia garinii by polymerase chain reaction (PCR) and electron microscopy (EM). METHODS: Report of a 67-year-old patient with medical history of recurrent iridocyclitis and arthritis presented with a bilateral, progressive, asymmetric crystalline keratopathy, which was particularly pronounced in the peripheral temporal superior cornea. After penetrating keratoplasty, crystalline keratopathy with stromal haziness recurred. Corneal regrafting was performed. The corneal specimen from the penetrating keratoplasty was examined by light and EM as well as by PCR. RESULTS: In the explanted corneal graft, as well as retrospectively in the corneal specimen from the first keratoplasty, spirochetelike bodies and fragments were detected by light and EM. Borrelia burgdorferi sensu lato DNA was demonstrated by broad-range (16S rDNA) PCR. A more precise identification as Borrelia garinii serotype 5 was possible by analyses of the flaB and ospA gene sequences. Borrelia-specific serological tests showed borderline titers in immunofluorescence and weak reaction in immunoblot, respectively. CONCLUSIONS: This case illustrates that borreliae must be considered as a cause of crystalline keratopathy; Borrelia-specific serological tests can be false negative; explanted cornea specimens of etiologically unclear crystalline keratopathy should be analyzed by EM or PCR for detection of pathogens; and prolonged antibiotic treatment might be effective to prevent progression or recurrence of the disease.

Corrugated Bruch's membrane in high myopia.

PURPOSE: To assess the appearance of Bruch's membrane (BM) in axially elongated eyes. METHODS: The light-microscopical investigation included histological anterior-posterior sections of human eyes. Using a light microscope, we assessed whether BM in the posterior segment was straight or locally corrugated. Corrugation of BM was defined as an elevation of BM with a height >20 µm over a basis of 50 µm without collateral proliferations of retinal pigment epithelium or choroidal swelling. RESULTS: The investigation included 85 eyes (age: 62.0 ± 14.1 years; axial length: 26.7 ± 3.5 mm). In multivariate analysis, the presence of a corrugated BM, detected in eight eyes (9.4%), was strongly associated with the presence of macular BM defects [p = 0.001; odds ratio (OR): 418; 95% confidence interval (CI): 1 215 000], but not with axial length (p = 0.54). Bruch's membrane (BM) corrugation was detected in seven (54%) of 13 eyes with macular BM defects. The single eye with BM corrugation and without macular BM defect showed the corrugated BM located in the parapapillary region at the peripheral end of a large parapapillary gamma zone. CONCLUSION: Bruch's membrane (BM) corrugation can be present in the vicinity of macular BM defects in highly myopic eyes, perhaps due to differences in the tension within BM in various regions at the margin of the BM defect. Bruch's membrane (BM) corrugation may also develop at the papillary end of BM in eyes with a large parapapillary gamma zone, potentially due to a disinsertion of BM at the end of the peripapillary choroidal border tissue of Jacoby. The observation of BM corrugation may help elucidating the aetiology of axial myopia.

Retinal pigment epithelium cell density in relationship to axial length in human eyes.

PURPOSE: To assess associations between axial length and density of retinal pigment epithelium (RPE) cells in various ocular regions. METHODS: The histomorphometric investigation included histological sections of enucleated eyes of Caucasian patients. Using a light microscope, we counted the number of RPE cells on Bruch's membrane at the ora serrata, in the pre-equatorial region, the equatorial and retro-equatorial region, at the midpoint equator/posterior pole, and at the posterior pole. RESULTS: The study included 65 globes with a mean axial length 25.9 ± 3.5 mm (range: 21.0-34.0 mm). Retinal pigment epithelium (RPE) cell count in the equatorial to retro-equatorial region (p < 0.001; correlation coefficient r2 : 0.44), in the pre-equatorial region (p < 0.001; r2 : 0.39) and at the midpoint equator/posterior pole (p = 0.03; r2 : 0.12) decreased with increasing axial length. Retinal pigment epithelium (RPE) cell count at the ora serrata (p = 0.49) and posterior pole (p = 0.44) was not significantly correlated with axial length. As a corollary, mean RPE cell density was higher (p < 0.001) at the posterior pole than at the midpoint equator/posterior pole or at the ora serrata region, where it was higher than in pre-equatorial region (p < 0.001) and in the equatorial to retro-equatorial region (p < 0.001). CONCLUSIONS: The decrease in the RPE cell density mainly in the equatorial to retro-equatorial region in association with longer axial length suggests a region of enlargement of Bruch's membrane in the equatorial to retro-equatorial area in association with axial elongation. The finding may be of interest to elucidate the process of emmetropization/myopization.

Histologic differences between primary high myopia and secondary high myopia due to congenital glaucoma.

PURPOSE: To search for histomorphometric differences between eyes with primary high myopia (PHM) or secondary high axial myopia (SHM) caused by congenital glaucoma, and non-highly myopic eyes (NHM). METHODS: Histologic anterior-posterior sections were histomorphometrically examined. RESULTS: The investigation included 58 human globes (mean age: 61.5 ± 18.5 years; axial length: 27.3 ± 4.0 mm; range: 21.0-39.0 mm). Bruch's membrane thickness was thinner in SHM than in PHM (posterior pole: p = 0.007; parapapillary region: p = 0.007); midpoint posterior pole/equator = 0.05) and thinner in SHM than in NHM (all p < 0.04), while PHM and NHM did not differ (all p > 0.50). Choroidal thickness did not differ (all p ≥ 0.40) at any measurement location between SHM and PHM, and was thinner (p < 0.05) in both myopic groups than in NHM. Posterior sclera was thinner (p < 0.001) in both myopic groups than in NHM, with no significant difference between both myopic groups. Pars plana scleral thickness was thinner (p = 0.02) in SHM than in PHM after adjusting for axial length. Scleral volume (p = 0.41) and choroidal volume (p = 0.74) did not differ between any of the groups. CONCLUSIONS: Thinning of Bruch's membrane overall is typical for SHM while eyes with PHM have a normal Bruch's membrane thickness. It may point to Bruch's membrane as an active part in the process of emmetropization/myopization. SHM in contrast to PHM showed scleral thinning in the pars plana region suggesting that the process of emmetropization/myopization takes place posterior to the pars plana. Both SHM and PHM unspecifically showed an axial length associated with thinning of choroid and posterior sclera, while both myopic groups did not differ with NHM in choroidal and scleral volume.

Retinal Thickness and Axial Length.

PURPOSE: To examine the relationships between axial length and foveal and peripheral retinal thickness. METHODS: Using optical coherence tomography, foveal retinal thickness was measured in participants of the population-based Beijing Eye Study without optic nerve or macula diseases. Inner and outer nuclear layer thickness as surrogate for retinal thickness was assessed in the fundus periphery in human globes enucleated due to malignant uveal melanoma or painful glaucoma. RESULTS: The study included 1117 individuals with a mean age of 64.2 ± 9.7 years (range: 50-93 years) and mean axial length of 23.4 ± 1.04 mm (range: 20.29-28.68 mm). In multivariate analysis, thicker central foveal thickness was associated with male sex (P < 0.001; standardized regression coefficient beta: -0.13; nonstandardized regression coefficient B: -5.84; 95% confidence interval (CI): -8.56, -3.13); urban region of habitation (P = 0.02; beta: 0.07; B: 3.56; 95% CI: 0.55, 6.57); thinner lens thickness (P = 0.01; beta: -0.08; B: -5.11; 95% CI: -9.01, -1.21); thinner subfoveal choroidal thickness (P = 0.04; beta: -0.07; B: -0.01; 95% CI: -0.03, -0.001); and longer axial length (P < 0.001; beta: 0.18; B: 3.79; 95% CI: 2.41, 5.17). In the same multivariate model, superior, inferior, and temporal foveal thickness was not significantly associated with axial length (P = 0.26, P = 0.19, P = 0.08, respectively), while thicker nasal foveal thickness was associated with longer axial length (P = 0.009; beta: 0.09; B: 1.50; 95% CI: 0.37, 2.62). In the histomorphometric part of the study including 32 eyes (sagittal diameter: 27.0 ± 4.2 mm; range: 22-37 mm), mean thickness of the inner and outer nuclear layers at the equator and at the midpoint equator/posterior pole decreased with longer axial length (P = 0.004; beta: -0.48; and P = 0.02; beta: -0.44, respectively). CONCLUSIONS: Myopic axial globe elongation was associated with retinal thinning in the equatorial and pre-equatorial region, while foveal retinal thickness was mostly unaffected by axial length. It suggests that axial elongation takes place predominantly in the equatorial and pre-equatorial region of the eye.

Central corneal thickness and thickness of the lamina cribrosa in human eyes.

PURPOSE: Since central corneal thickness may inversely influence the amount and rate of progression of glaucomatous optic nerve damage and because lamina cribrosa thickness may be of importance in susceptibility to glaucoma, it was the purpose of the present study to evaluate whether central corneal thickness is related to lamina cribrosa thickness. METHODS: The histomorphometric study included 111 enucleated nonglaucomatous eyes of 111 white subjects. On anterior-posterior histologic sections through the pupil and the central optic disc region, the thickness of the cornea, lamina cribrosa, and peripapillary sclera and the shortest distance between the intraocular space and the cerebrospinal fluid space were measured. Axial length ranged between 20 and 32 mm. RESULTS: Mean central corneal thickness (mean +/- SD: 616.6 +/- 108.3 microm) and mean central lamina cribrosa thickness (378.1 +/- 117.8 microm) were statistically independent of each other (P = 0.15; correlation coefficient, r = 0.14). In a similar manner, lamina cribrosa thickness at the optic disc border was statistically independent of central corneal thickness (P = 0.51; r = 0.06) and peripheral corneal thickness (P = 0.34; r = 0.09). In a parallel way, peripapillary scleral thickness (P = 0.84) and the shortest distance between the prelaminar space and cerebrospinal fluid space (P = 0.10) were statistically independent of central corneal thickness. CONCLUSIONS: In nonglaucomatous human globes, central corneal thickness may not correlate significantly with lamina cribrosa thickness, peripapillary scleral thickness, and shortest distance between intraocular space and cerebrospinal fluid space. Histologic artifact and sectioning methods could partially account for the lack of an association. The study results may suggest clinically that an assumed relationship between central corneal thickness and susceptibility to glaucoma cannot be explained by an anatomic correspondence between corneal thickness and histomorphometry of the optic nerve head.

The Pathogenesis of floppy eyelid syndrome: involvement of matrix metalloproteinases in elastic fiber degradation.

OBJECTIVE: To investigate histopathologic alterations of eyelid biopsy specimens from patients with floppy eyelid syndrome (FES) with special regard to elastic fiber content and ultrastructure as well as to the expression of elastin-degrading enzymes to elucidate the pathogenesis of this disorder. DESIGN: Retrospective, interventional case series. PARTICIPANTS AND CONTROLS: Eleven consecutive patients with FES and 10 age-matched control patients with basal cell carcinoma of the eyelid. METHODS: Horizontal pentagonal eyelid resections of 16 upper lids were performed in 11 patients with FES. Full-thickness eyelid biopsy specimens from study and control patients were examined by light and transmission electron microscopy, semiquantitative morphometry, and immunohistochemistry using antibodies against matrix metalloproteinase (MMP)-2, MMP-7, MMP-9, and MMP-12 and neutrophil elastase. RESULTS: All patients treated with surgical horizontal eyelid shortening were asymptomatic at follow-up. Histopathologic analysis of the surgical specimens showed, apart from unspecific signs of chronic inflammation, a significant decrease in the amount of elastin within the tarsal plate and eyelid skin as compared with controls. Residual elastic fibers revealed an abnormal ultrastructure with a diminished elastin core. Immunohistochemistry demonstrated an increased immunoreactivity for elastolytic proteases, particularly MMP-7 and MMP-9, in areas of elastin depletion in FES specimens as compared with controls. CONCLUSIONS: The findings indicate that upregulation of elastolytic enzymes, most probably induced by repeated mechanical stress, participates in elastic fiber degradation and subsequent tarsal laxity and eyelash ptosis in FES.