Childhood versus early-teenage onset Leber's hereditary optic neuropathy: visual prognosis and capacity for recovery.

OBJECTIVE: In Leber's hereditary optic neuropathy (LHON) in children and teenagers, the influence of age on visual prognosis has not yet been investigated. METHODS: Patients from the mitoNET registry with LHON onset at age 4-16 years with at least 4 years of follow-up without treatment were included. Visual acuity (VA) at baseline, lowest VA ever recorded (nadir) and VA at end of follow-up were compared between childhood onset (ChO, ≤12 years of age) and early-teenage onset (eTO; 13-16 years). RESULTS: Out of 231 patients with LHON, 19 met the inclusion criteria (8.2%). There were 11 patients in the ChO and 8 patients in the eTO group. Mean age at onset was 8.6 (SD 2.1) years (ChO) and 15.4 (SD 0.7) years (eTO) (p<0.00001). Follow-up was mean 184 (SD 129) months (ChO) and 119 (SD 78) months (eTO) (p=0.22). Baseline VA was similar between both groups in better (p=0.96) and worse eyes (p=0.54). In worse eyes, both groups deteriorated similarly (p=0.79) until nadir and showed similar recovery until end of follow-up (p=0.38). In better eyes, both groups deteriorated similarly (p=0.16) until nadir. From nadir until end of follow-up, better eyes in the ChO group showed a significantly better recovery (-0.35 (SD 0.36) vs -0.01 (SD 0.06) logMAR; p=0.02) than eTO eyes. CONCLUSION: Visual prognosis of LHON in children is much more favourable in cases of childhood onset (≤12 years of age) as compared with teenage onset (13-16 years), mostly due to better recovery from nadir in childhood onset.

[Tear Film Osmolarity in Normal Individuals: Comparison of Two Osmometers]. / Tränenfilmosmolarität gesunder Probanden: Vergleichbarkeit zweier Osmometer.

INTENTION: The hyperosmolarity of the tear film is an important clinical sign of dry eye disease. It is the most important diagnostic parameter. In addition to the TearLab osmometer (TearLab Corp, San Diego, CA), which has been available for several years, the I-Pen osmometer (I-MED Pharma Inc, Dollard-des-Ormeaux, Quebec, Canada) has been recently marketed. The intention of our study was to compare tear film osmolarities in normal individuals as measured by TearLab and I-Pen. METHODS: 51 healthy subjects (mean age 40.6 years, range 17 - 63 years, 66.7% females) without dry eye disease (ocular surface disease index < 13, tear film break-up time > 7 s, normal Schirmer test > 10 mm/5 min) were included in this study. Tear film osmolarity was measured in the tear meniscus (TearLab) and the palpebral conjunctiva (I-Pen) with a 30 min interval. The osmolarity testing techniques were alternated. Statistical analysis was performed using Wilcoxon tests and Spearman correlations. RESULTS: Mean TearLab osmolarities were 295.1 mosmol/l (right eye), 294.0 mosmol/l (left eye), and 294.6 mosmol/l (mean of both eyes) with a range of 268 to 394 mosmol/l. I-Pen measured mean osmolarites of 301.6 mosmol/l (right eye), 302.5 mosmol/l (left eye), and 302.1 mosmol/l (mean of both eyes) with a range of 276 to 394 mosmol/l. There was a significant difference in tear film osmolarities for the two techniques for both single eyes (p < 0.02) and the mean value of both eyes (p < 0.001). TearLab and I-Pen measurements did not correlate significantly in any eye (r = 0.27 and r = 0.08 for right and left eye, respectively). With a cut-off value of 308 mosmol/l (as suggested for TearLab), 98.0% of TearLab values and 68.6% of I-Pen values were in the normal range. CONCLUSIONS: I-Pen measured significantly higher tear film osmolarities than TearLab. The location of the measurement site in the palpebral conjunctiva could be responsible for this difference. Our results indicate that cut-off values should be changed when using I-Pen for evaluation of tear film osmolarity. Further examinations and studies with greater cohorts of healthy subjects and patients suffering from dry eye disease are necessary.

VITRECTOMY FOR INTERMEDIATE AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH TANGENTIAL VITREOMACULAR TRACTION: A CLINICOPATHOLOGIC CORRELATION.

PURPOSE: To describe the morphologic characteristics of the vitreomacular interface in intermediate age-related macular degeneration associated with tangential traction due to premacular membrane formation and to correlate with optical coherence tomography (OCT) findings and clinical data. METHODS: Premacular membrane specimens were removed sequentially with the internal limiting membrane from 27 eyes of 26 patients with intermediate age-related macular degeneration during standard vitrectomy. Specimens were processed for immunocytochemical staining of epiretinal cells and extracellular matrix components. Ultrastructural analysis was performed using transmission electron microscopy. Spectral domain optical coherence tomography images and patient charts were evaluated in retrospect. RESULTS: Immunocytochemistry revealed hyalocytes and myofibroblasts as predominant cell types. Ultrastructural analysis demonstrated evidence of vitreoschisis in all eyes. Myofibroblasts with contractile properties were observed to span between folds of the internal limiting membrane and vitreous cortex collagen. Retinal pigment epithelial cells or inflammatory cells were not detected. Mean visual acuity (Snellen) showed significant improvement from 20/72 ± 20/36 to 20/41 ± 20/32 (P < 0.001) after a mean follow-up period of 19 months (median, 17 months). During this period, none of the eyes required anti-vascular endothelial growth factor therapy. CONCLUSION: Fibrocellular premacular proliferation in intermediate age-related macular degeneration predominantly consists of vitreous collagen, hyalocytes, and myofibroblasts with contractile properties. Vitreoschisis and vitreous-derived cells appear to play an important role in traction formation of this subgroup of eyes. In patients with intermediate age-related macular degeneration and contractile premacular membrane, release of traction by vitrectomy with internal limiting membrane peeling results in significantly functional and anatomical improvement.

Assessment of intravitreal ocriplasmin treatment for vitreomacular traction in clinical practice.

PURPOSE: To assess treatment effects following intravitreal injection of ocriplasmin for vitreomacular traction (VMT), with or without full-thickness macular hole (FTMH), in real-life setting. METHODS: This is a monocentric, retrospective, consecutive series of 82 eyes from 82 patients who underwent ocriplasmin treatment between July 2013 and December 2016. We included 57 eyes with pure VMT, 17 eyes with small FTMHs, and eight eyes with medium FTMHs. Primary outcome measures were VMT release and MH closure rates. Secondary outcomes were visual acuity (VA), morphological changes, and subjective visual impairment after 1, 3, and 6 months and at last follow-up. RESULTS: After a median follow-up of 10 months, VMT release was achieved by pharmacologic vitreolysis in 57% of all eyes, whereas the macular hole closure rate was 32%. In those presenting with five or more positive prognostic factors (PPF), eyes with pure VMT showed nonsurgical traction release in 88%, and FTMHs were released in 93%, with a closure rate of 20%. Small FTMHs closed in 41% and medium FTMHs in 13%. The mean change in VA (LogMAR) was -0.07 ± 0.24 (median - 0.10) in all eyes. Subretinal fluid accumulation and ellipsoid zone changes were seen in 31% and 37% of all eyes, respectively. They were more frequent in eyes with traction release, but were self-limited. CONCLUSIONS: In a real-life setting, release of VMT by ocriplasmin injection can be achieved in the majority of eyes, relying on a strict patient selection. Closure of FTMHs rather correlates with hole diameter than with presence of PPF, and remains a rare finding in medium FTMHs.

Evaluation of a short-term topical interferon α-2b treatment for histologically proven melanoma and primary acquired melanosis with atypia.

OBJECTIVE: To evaluate the efficiency of series of 6-week treatments with brief intervals (6-week = 1 cycle) of topical Interferon α-2b (IFNα-2b) treatment in primary acquired melanosis (PAM) with atypia and melanoma of the conjunctiva. PATIENTS AND METHODS: Five patients with biopsy-proven PAM with atypia and seven patients with melanoma of the conjunctiva, treated with topical IFNα-2b (1 million units/ml, 5 times daily), were included in the study. All patients had colour photographs and the tumour area was measured manually for each patient before and after treatment. RESULTS: The median age of 12 patients at initiation of treatment was 61.5 years (range 39-75 years). The mean therapy duration was 2.4 cycles (range 1-6 cycle). Compared to pretreatment lesion dimension, the mean decrease in tumour size were after the first cycle 66% (range 18-98%; p = 0.004; n = 10 patients), after the second cycle 55% (range 10-100%; p = 0.016; n = 7 patients), and after the third cycle 74% (range 23-100%; n = 3 patients). In one patient 6 cycles of topical IFNα-2b were needed. The decrease in size was 22% after the 4(th) cycle, 34% after the 5(th) cycle, and 98% after the 6(th) cycle. CONCLUSION: Our clinical experience demonstrates promising results of topical IFNα-2b treatment for PAM with atypia and melanoma of the conjunctiva without any local or systemic side effects. However, future multicenter prospective studies are recommended to confirm the efficiency and safety of topical IFNα-2b treatment.

MuSIC report III: tumour microcirculation patterns and development of metastasis in long-term follow-up of melanocytic uveal tumours.

PURPOSE: To statistically determine differences in microcirculation patterns between nevi and uveal melanomas and the influence of these patterns on metastatic potential in the long-term follow-up of 112 patients with melanocytic uveal tumours. In vivo markers indicating malignancy and metastatic potential have implications for treatment decision. METHODS: Primary diagnosis and work-up included clinical examination, fundus photography, standardized A and B scan echography as well as evaluation of tumour microcirculation patterns via confocal fluorescein and indocyanine green angiography (ICGA). Patient data were collected from the patient files, the tumour registry or personal contact. Statistical analysis was performed with spss 22.0 using chi-square, Fisher's exact test and Kaplan-Meier survival analysis. RESULTS: Forty-three uveal melanocytic lesions remained untreated and were retrospectively classified as benign nevi, whereas 69 lesions were malignant melanomas (T1: 32, T2: 28, T3: 6 and T4: 3). 'Silent' and 'arcs without branching' were found significantly more often in nevi (p = 0.001 and p = 0.010), whereas 'parallel with cross-linking' and 'networks' were significantly more frequent in melanomas (p = 0.022 and p = 0.029). The microcirculation pattern 'parallel with cross-linking' proved significantly more frequent in patients who developed metastases (p = 0.001). CONCLUSIONS: Certain microcirculation patterns may guide us in differentiating uveal nevi from malignant melanomas. A non-invasive prognostic marker can be of great value for borderline lesions in which cytology is less likely taken. 'Parallel with cross-linking' did not only indicate malignancy, but it was also associated with later tumour metastasis.

Cells at the vitreoretinal interface in small full-thickness macular holes.

PURPOSE: To report on total number, distribution, and type of cells at the vitreomacular interface in small full-thickness macular holes. METHODS: Internal limiting membrane specimens were removed from 20 consecutive patients with macular holes <250 µm at times when pharmacologic vitreolysis was not available. Specimens were flat mounted and investigated by phase contrast and interference microscopy and immunocytochemistry. Clinical data were documented including optical coherence tomography analysis using the caliper function. Thirteen antibodies were used for glial cells, hyalocytes, macrophages, retinal pigment epithelial cells, different types of collagen, alpha-smooth muscle actin, and proliferating cells. RESULTS: There was a positive correlation between macular hole size and cell density at the internal limiting membrane (Spearman's Rho: r = 0.519, P = 0.019). Mostly, single glial cells were found on the internal limiting membrane. In five patients, cell clusters were present. There was a strong immunoreactivity for glial cell markers. Immunoreactivity of hyalocyte markers, alpha-smooth muscle actin, and Ki-67 was found in cell clusters but otherwise sparse. CONCLUSION: Single cells of glial origin without signs of proliferation or contraction are present in eyes with small full-thickness macular holes. In some eyes, however, clusters of cells can be seen, capable of proliferation and exerting tangential traction. Our findings emphasize the need for better visualization of the vitreoretinal pathology by optical coherence tomography, especially to distinguish between single cells and cell clusters.

Epiretinal membrane characteristics correlate with photoreceptor layer defects in lamellar macular holes and macular pseudoholes.

PURPOSE: To report on epiretinal membrane (ERM) characteristics and photoreceptor layer integrity of lamellar macular holes (LMHs) and macular pseudoholes (MPHs), and to compare with clinical course in operated and untreated eyes. METHODS: We consecutively reviewed the charts of patients with LMH and MPH between 2003 and 2013. For clinical analysis, we included 87 eyes (48 with LMH, 39 with MPH) with a minimum follow-up of 6 months. Of these, we included 64 eyes (37 with LMH, 27 with MPH) for high-resolution spectral domain optical coherence tomography analysis with examinations fulfilling the required resolution and quality of optical coherence tomography images. Epiretinal membranes were termed "typical tractional ERM" if presenting with contractive properties, or "atypical epiretinal tissue" if presenting as epiretinal material of homogeneous medium reflectivity without contractive properties. Integrity or discontinuity of the inner and outer segment (IS/OS) and the external limiting membrane (ELM) was evaluated by differentiating between "defect present" and "defect absent." RESULTS: In eyes with LMH, atypical epiretinal tissue presented in 29%, typical tractional ERMs were seen in 57%, and a combination of both in 14%. In contrast, eyes with MPH rarely presented atypical epiretinal tissue, and typical tractional ERMs were found in 89%. Comparing cases with LMH, eyes with atypical epiretinal tissue showed significantly more defects of the IS/OS and the ELM than eyes with typical tractional ERM. Both IS/OS and ELM defects correlated with a significant lower best-corrected visual acuity. Defects of the IS/OS were seen in 41% of LMH and 11% of MPH. Defects of the ELM revealed in 27% of LMH and in 11% of MPH. Operated eyes with disrupted IS/OS but intact ELM had significant better best-corrected visual acuity than eyes with defects in both layers. CONCLUSION: Atypical epiretinal tissue is related to the presence of photoreceptor layer defects and to poor visual acuity. It seems that integrity of the ELM is most important for functional recovery after surgery in both LMH and MPH. The presence of atypical epiretinal tissue in eyes with LMH may represent differences in the pathogenesis compared with MPH, and might have therapeutic implications for the proceeding with macular surgery in selected cases.

Hyalocytes in idiopathic epiretinal membranes: a correlative light and electron microscopic study.

PURPOSE: To describe characteristics of epiretinal cells at the vitreoretinal interface by correlative light and electron microscopy (CLEM). METHODS: Epiretinal membrane (ERM) specimens and internal limiting membrane (ILM) specimens were harvested by sequential peeling during vitrectomy from 27 eyes with idiopathic epiretinal gliosis, and processed for CLEM. Intraoperatively, the presence of posterior vitreous detachment (PVD) was documented. We used anti-vimentin, anti-α-smooth muscle actin (α-SMA), and anti-CD45 as primary antibodies. A fluorescein-tagged immunonanogold cluster was used as secondary antibody and visualized under the fluorescence and transmission electron microscope. RESULTS: We demonstrated CD45-positive cells specifically labelled at their plasma membranes with ultrastructural features known for hyalocytes, such as oval nucleus with marginal chromatin, vacuoles, dense granules, and thin cytoplasmic protrusions. CD45-positive cells were mostly located on a thick layer of native vitreous collagen. They were covered by newly formed collagen strands with multilayered proliferation of myofibroblasts. We also demonstrated immunoreactivity for vimentin and alpha-SMA. Cell fragments with positive labelling for α-SMA and vimentin were not only found on the vitreal side of the ILM, but also on the retinal side. CONCLUSIONS: By CLEM, the majority of CD45-positive cells in epiretinal cell proliferation were characterized as hyalocytes. In the context of anomalous PVD and vitreoschisis, ultrastructural features and topographic localization of hyalocytes suggest that these cells play a significant role in ERM formation. CLEM enables a more accurate characterization of epiretinal cell proliferation, and therefore, contributes to a better understanding of the pathogenesis of diseases at the vitreoretinal interface.

Perioperative and postoperative risk factors for corneal graft failure.

PURPOSE: In this study, we assessed the outcome of penetrating keratoplasties using organ-cultured corneal tissues at the University Eye Hospital, Ludwig-Maximilians-University, Munich, Germany. The goal was to identify perioperative and postoperative risk factors that may affect graft survival. PATIENTS AND METHODS: The medical records of 377 patients who underwent a penetrating keratoplasty between 2001 and 2011 were reviewed. Organ-cultured corneal tissue was obtained from the eye bank of Ludwig-Maximilians-University. Perioperative and postoperative risk factors for graft failure were evaluated by univariate and multivariate analyses. RESULTS: The 5-year overall survival rate of penetrating keratoplasties was 68%. Graft failure occurred in 26% of patients. High-risk keratoplasties, such as repeat penetrating keratoplasties and emergency penetrating keratoplasties, as well as postoperative conditions, such as glaucoma, retinal surgery, suture problems, persistent epithelial defect, infectious keratitis, and graft rejection, were significantly associated with graft failure in the multivariate analyses. CONCLUSION: This study showed a similar graft-survival rate as demonstrated in previous studies. In addition, a number of perioperative and postoperative risk factors were identified in this specific patient population.

Donor-related risk factors and preoperative recipient-related risk factors for graft failure.

PURPOSE: The aim of this study was to evaluate the outcome of penetrating keratoplasties, at the University Eye Hospital, Ludwig-Maximilians-University, Munich, Germany, using organ-cultured donor corneas and to identify preoperative risk factors, which may influence the event of graft failure. METHODS: In this study, 377 medical records of patients, who underwent penetrating keratoplasty between 2001 and 2011, were reviewed. Organ-cultured donor corneas were obtained from the eye bank, Ludwig-Maximilians-University, Munich, Germany. Donor-related and preoperative recipient-related risk factors for graft failure were analyzed by univariate and multivariate analyses. RESULTS: Graft failure occurred in 26% of patients. The following preoperative factors were significantly associated with graft failure by multivariate analyses: high donor age, low donor endothelial cell density, high patient age, indications of infectious keratitis, acute perforation of noninfectious keratitis, prior graft failure, chemical burn, trauma, glaucoma-associated corneal decompensation, high-risk graft indications, corneal edema, anterior chamber lens, diabetes mellitus, atopy, and autoimmune diseases. CONCLUSIONS: This study demonstrated a success rate of 74%, which is consistent with previous studies. Various preoperative recipient-related factors seem to influence the outcome of penetrating keratoplasties, whereas few donor-related factors have a significant association with graft failure.

Factors affecting the use of antioxidant supplements in patients with late AMD.

BACKGROUND: The purpose of this study was to assess the use of oral antioxidant supplements in patients with late age-related macular degeneration (AMD) and to identify influencing factors that may affect the use of such supplements. METHODS: The study included 47 patients with late AMD. Using a questionnaire, the patients were asked for their demographic, ophthalmologic, and systemic data, their source of recommendation of antioxidant use for AMD, and/or their reasons for nonuse. The demographic, ophthalmologic, and systemic information was correlated with use or nonuse of oral antioxidant supplements for AMD. RESULTS: Sixty-eight percent (32/47) of patients took antioxidant supplements for AMD and 32% (15/47) of patients did not. There were no statistically significant differences in demographic, ophthalmologic, and systemic parameters between patients with late AMD who used supplements and those who did not. Two thirds of patients with late AMD (66%, 31/47) reported being recommended oral antioxidant supplements for AMD by their ophthalmologist. Patients who did not use antioxidant supplements either did not obtain any recommendation or did not believe in their benefits. CONCLUSION: This study shows that most patients with late AMD use antioxidant supplements despite the recommendation to do so being missing in the Age-Related Eye Disease Study. Our study emphasizes the importance of seeking further therapeutic options for patients with late AMD.

Evaluation of intraocular pressure elevation after multiple injections of intravitreal ranibizumab.

BACKGROUND: We wanted to determine whether multiple injections of intravitreal ranibizumab was associated with an elevated intraocular pressure (IOP) in patients treated for neovascular age-related macular degeneration (AMD). METHODS: This retrospective study examined 53 patients with neovascular AMD treated with multiple injections of intravitreal ranibizumab. The main outcome measure was the difference in IOP between the frequently-treated study eyes (≥15 injections) and the unfrequently-treated fellow control eyes (≤ five injections). Patients were divided into three study groups: group I (35 patients with 15 to 19 injections); group II (15 patients with 20 to 29 injections); and group III (three patients with ≥30 injections). The IOP was measured by Goldmann applanation tonometry 4 weeks after the last injection of intravitreal ranibizumab. For statistical analysis, the IOP was then correlated with the number of ranibizumab injections. RESULTS: Among the frequently-treated study eyes, the mean IOP was 13.68±2.91 mmHg (range, 8 to 20 mmHg). The unfrequently-treated fellow control eyes had a mean IOP of 13.45±3.09 mmHg (range, 9 to 25 mmHg). There was no significant correlation of the IOP difference between the study and control eyes with the number of ranibizumab injections (correlation coefficient 0.77; P=0.583). For each of groups I, II, and III, the difference in mean IOP between the study and control eyes was nonsignificant (P>0.05). There was also no significant association of the IOP difference between the study and control eyes with the number of ranibizumab injections for each group (P=0.391). CONCLUSION: Our study did not find an increased IOP in frequently-ranibizumab-treated eyes when compared to unfrequently-treated fellow control eyes. Further studies with a greater sample size are needed to evaluate whether an increased number of ranibizumab injections is associated with IOP changes.

Factors influencing self-reported use of antioxidant supplements in patients with age-related macular degeneration.

AIM: The goals of the present study were to evaluate the current use and accuracy of dose-taking prescription among patients with age-related macular degeneration (AMD) and to detect potential factors influencing the use or non-use of oral antioxidant supplements. MATERIALS AND METHODS: This is a cross-sectional questionnaire-based study of 65 patients with AMD of Age-Related Eye Disease Study (AREDS) category 3 (intermediate AMD) or category 4 (unilateral advanced AMD). Self-report data were obtained from a structural clinical interview in clinic. The patients were asked questions regarding their demographic, ophthalmologic and systemic data, their source of recommendation for antioxidant supplement use and/or their reasons for non-use. Afterwards, this information was correlated with the use or non-use of antioxidant supplements. Statistical analyses were conducted using a series of Mann-Whitney U-tests and Fisher's exact tests. RESULTS: There were 55.4% (36 of 65) of the patients reporting antioxidant supplement use for AMD and 44.6% (29 of 65) with no supplement use. However, only 56.7% (17 of 30) took the recommended dose on label. There were significantly more female patients taking supplements than male patients (p = 0.010). A statistically significant correlation was also found between supplement use and the number of visits to an ophthalmologist per year (p = 0.037). The main reason for antioxidant supplement non-use was the missing awareness of the availability of antioxidant supplements. CONCLUSIONS: Despite the recommendation of oral antioxidant supplements in the ARED Study for patients with AMD of category 3 or 4, only about half of these patients took the supplements in this study. Identifying the factors, which influenced the decision against supplement use, may help to better support patients in the prevention of severe vision loss caused by AMD.

Epiretinal cell proliferation in macular pucker and vitreomacular traction syndrome: analysis of flat-mounted internal limiting membrane specimens.

PURPOSE: To describe new details of epiretinal cell proliferation in flat-mounted internal limiting membrane specimens. METHODS: One hundred nineteen internal limiting membrane specimens were removed en bloc with epiretinal membranes from 79 eyes with macular pucker (MP) and 40 eyes with vitreomacular traction syndrome. Intraoperatively, posterior vitreous detachment was assessed as complete or incomplete. Whole specimens were flat-mounted on glass slides and processed for interference and phase-contrast microscopy, cell viability assay, and immunocytochemistry. RESULTS: Mean cell viability percentage was higher in MP than in vitreomacular traction syndrome. Two cell distribution patterns were found. Anti-CD163 labeling presented predominantly in MP with complete posterior vitreous detachment. CD45 expression was similar in all groups of diagnosis. Anti-glial fibrillary acidic protein (GFAP) labeling was found in MP irrespective of the extent of posterior vitreous detachment. Alpha-SMA (α-smooth muscle actin) labeling was mainly presented in MP with incomplete posterior vitreous detachment and in vitreomacular traction syndrome. Simultaneous antibody labeling included GFAP/CD45, GFAP/CD163, CD163/CD45, and CD163/α-SMA. CONCLUSION: Hyalocytes constitute a major cell type of epiretinal cell proliferation in eyes with MP and vitreomacular traction syndrome. Glial cells, notably retinal Muller cells, are involved as well. It appears that transdifferentiation of cells in vitreomacular traction might be more frequent than previously thought and that those cells possess a greater variability of immunocytochemical properties than expected.

Immunocytochemical and ultrastructural evidence of glial cells and hyalocytes in internal limiting membrane specimens of idiopathic macular holes.

PURPOSE: To provide new information on epiretinal cell proliferation and the cells' origin in idiopathic macular holes and to overcome the effects of embedding and sectioning preparation procedures on cell-distribution patterns. METHODS: Interference and phase-contrast microscopy, immunocytochemistry, and scanning and transmission electron microscopy were performed on surgically excised whole-mounted internal limiting membrane (ILM) specimens removed from 60 eyes with idiopathic macular holes. Cell distribution and cell morphology were correlated with immunocytochemical staining characteristics. Twelve cell type-specific antibodies were used to detect glial cells, hyalocytes, retinal pigment epithelial cells, retinal ganglion cells, and immune cells. Cell viability was analyzed. RESULTS: Epiretinal cell proliferation was found in all ILM specimens, irrespective of the stage of the macular hole. Cell density showed a broad variety. Immunocytochemistry frequently revealed simultaneous expression of GFAP/CD45, GFAP/CD64, GFAP/CD68, GFAP/CRALBP, and GFAP/CD90. Some cells presented with intracellular contractile filaments (anti-αSMA); others were not immunoreactive to any antibody examined. The percentage of viable cells showed a broad variety with a mean of 73% (SD 29%). Electron microscopy demonstrated glial cells, hyalocytes, and myofibroblast-like cells. CONCLUSIONS: The presence of epiretinal cells at the ILM in all macular hole stages strongly suggests a substantial involvement of cell migration and proliferation in the course of macular hole development. Glial cells and hyalocytes play the predominant role in epiretinal cell proliferation. Given the co-expression of glial cell and hyalocyte markers, transdifferentiation of epiretinal cells needs further elucidation, especially with respect to αSMA-positive cells leading to traction at the vitreoretinal interface.

Receiver operating characteristic analysis: calculation for the marker 'melanoma inhibitory activity' in metastatic uveal melanoma patients.

The serological marker melanoma inhibitory activity (MIA) has been shown to be significantly higher in the serum of patients suffering from metastatic uveal melanoma than in progression-free patients. The objective of this study was to calculate a meaningful receiver operating characteristic (ROC) curve for MIA based on a large patient collective and to find an appropriate threshold value. MIA tumor marker levels of 503 outpatients suffering from uveal melanoma were evaluated using enzyme-linked immunosorbent assay. Fifty-four patients had confirmed metastases and 449 patients showed no overt metastatic disease at the time the blood sample was taken. ROC analysis was performed and the area under the curve (AUC) was calculated. Metastatic patients showed significantly higher MIA levels (median 11.69 ng/ml) than patients in the group without overt metastatic disease (median 6.97 ng/ml) (the Mann-Whitney test, P<0.001). The AUC was 0.84 (95% confidence interval: 0.76-0.91). The ROC resulting from our study can be applied for test comparison by means of AUC. The AUC value of 0.84 for MIA demonstrates the accurate performance of the test. On the basis of this ROC curve, we propose a MIA threshold value for uveal melanoma patients of 8.3 ng/ml (with a corresponding sensitivity of 82% and specificity of 77%, positive predictive value of 0.30 and negative predictive value of 0.97). In patients with higher MIA serum levels, further diagnostics should be initiated.

Vitrectomy does not increase the risk of open-angle glaucoma or ocular hypertension--a 5-year follow-up.

BACKGROUND: The goal of this study was to investigate the development of late onset open-angle glaucoma (OAG) or ocular hypertension after vitrectomy in phakic and pseudophakic eyes. METHODS: In this retrospective case series, the records of 441 patients who had undergone vitrectomy in one eye by a single surgeon were reviewed. The development of OAG or ocular hypertension in the vitrectomized and fellow control eyes was compared. Furthermore, the influence of the lens status (phakic or pseudophakic) on the onset of OAG or ocular hypertension in the vitrectomized and fellow control eyes was analysed. Additionally, the mean intraocular pressure (IOP) and the mean number of antiglaucomatous medications were calculated for both eyes. RESULTS: A mean follow-up period of 79.5 +/- 25.6 months was achieved. There were 19 vitrectomized eyes (4.31%) with postoperative OAG, and 19 vitrectomized eyes (4.31%) with postoperative ocular hypertension. Eleven control eyes (2.49%) had OAG, and 13 control eyes (2.95%) ocular hypertension. There were no statistically significant differences in the development of OAG or ocular hypertension between the vitrectomized and fellow control eyes. Furthermore, the lens status in vitrectomized eyes did not influence the late development of OAG or ocular hypertension. There were no significant differences in the mean IOP and the mean number of antiglaucomatous medications between the two eyes. CONCLUSIONS: Contrary to previous reports, we could not observe an increased incidence of late onset OAG or ocular hypertension after vitrectomy. Similarly, the removal of the lens did not increase the risk of OAG or ocular hypertension in vitrectomized eyes.

Two-step LASIK after penetrating keratoplasty.

PURPOSE: The point of interest of this retrospective case review is to study refractive changes caused by the hinged lamellar keratotomy and the refractive outcome after laser ablation in a second step within the scope of laser in situ keratomileusis (LASIK) in patients with penetrating keratoplasty. METHODS: Data from eight patients obtained before lamellar keratotomy, before laser ablation, and three months later were evaluated. Keratotomies were performed with the Moria((R)) LSK one and the Amadeus((R)) 2 microkeratome, laser ablation was performed with the Schwind((R)) Keratome I and the Wavelight((R)) Allegretto WaveEyeQ. RESULTS: Uncorrected visual acuity (UCVA) improved significantly from 1 [logMar] to 0.4 [logMar] at the last visit. Median gain of UCVA was 7.38 +/- 2.96 Snellen lines. Best spectacle-corrected visual acuity did not change significantly. Preoperative manifest refraction spherical equivalent decreased from -4.02 +/- 4.77 diopters (D) to -1.11 +/- 2.45 D after laser ablation. Mean preoperative manifest astigmatism was -7.27 +/- 3.65 D, after lamellar keratotomy -6.72 +/- 3.68 D, and after laser ablation -2.08 +/- 1.80 D. Manifest astigmatism did not change significantly after the keratotomy. CONCLUSIONS: Lamellar keratotomy causes biomechanical changes to the cornea. We favor a two-step LASIK in penetrating keratoplasty patients in order to improve precision and predictability of the refractive outcome.

Idiopathic macular holes: ultrastructural aspects of surgical failure.

PURPOSE: To investigate the ultrastructure of the internal limiting membrane (ILM) and epiretinal tissue in eyes with idiopathic macular holes that were not successfully closed by one operation. METHODS: A second vitrectomy with en bloc removal of the ILM and epimacular tissue was performed in 16 eyes with full-thickness macular holes after surgical failure. The specimens were processed for transmission electron microscopy. In 5 of 16 eyes, specimens of first macular hole surgery were also analyzed. RESULTS: Fibrocellular proliferation at the vitreal side of the ILM was found in all specimens from second vitrectomy. Myofibroblasts and fibroblasts were predominant. Cells were frequently observed as irregular accumulations rather than regular multilayers at the ILM. Masses of newly formed collagen were found distributed between cells and ILM. All specimens from first macular hole surgery were characterized by regular cellular layers and the presence of native vitreous collagen. CONCLUSIONS: Eyes with idiopathic macular holes that were found not to be closed early after the first vitrectomy show massive proliferation of cells and newly formed collagen irregularly distributed at the remaining ILM. After surgical intervention, ILM remnants and collagen may represent a stimulus for the early formation of tangential traction preventing successful macular hole closure.