[Statistical analysis of correlated measurement data in ophthalmology : Tutorial for the application of the linear mixed model in SPSS and R using corneal biomechanical parameters]. / Statistische Auswertung korrelierter Messdaten in der Augenheilkunde : Tutorial zur Verwendung des linear gemischten Modells in SPSS und R anhand biomechanischer Parameter der Hornhaut.

BACKGROUND: In ophthalmology data from both eyes of a person are frequently included in statistical analyses. As correlated data are used this procedure contradicts the independency principle for classical statistical tests, such as Student's t­test and analysis of variance (ANOVA). In this tutorial a new possibility is presented in which data from both eyes can be used for statistical analysis. OBJECTIVE: The statistical approach of linear mixed models (LMM) was used to take correlated data of both eyes of patients into account. METHODS: The LMM is available in several statistical software packages, e.g. SPSS and R, and allows the inclusion of measurement data from both eyes of a person in the statistical analysis. The application was tested on data from a biomechanical characterization of the cornea from healthy participants assessed with the dynamic Scheimpflug analyzer (Corvis ST; Oculus, Wetzlar, Germany). RESULTS: A total of 158 eyes from 79 healthy participants were included. A strong correlation between the right and left eyes of the participants could be observed with respect to the analyzed parameters. Comparison of the biomechanical parameters between the different age groups showed that P-values were increased when using the LMM compared to the ANOVA. Older participants (56-79 years) showed a significantly shorter time to the second applanation (P = 0.002), a significantly increased eyeball movement during the deformation (P = 0.001) and a significantly higher stiffness at the first applanation (P = 0.006) compared to younger participants (18-35 years). CONCLUSION: The analysis of measurement data from both eyes using classical statistical tests, without the consideration of the correlation, leads to an overestimation of the statistical power. This can be avoided by implementation of the LMM.

[Unusual coloboma of the optic disc?] / Ungewöhnliches Optikuskolobom?

A twelve-year old girl presented herself for a routine ophthalmologic examination in our clinic. Best-corrected visual acuity (BCVA) was 1.0 on both eyes. On funduscopic examination we saw a yellow round structure inferior to the optic nerve head. In optical coherence tomography (OCT) examination the structure showed cupping and opening of the Bruch membrane and retinal pigment epithelium (RPE). Visual field testing revealed an absolute scotoma right in the area were the abnormal coloboma was localized. We diagnosed a pseudo-doubling of the optic disk, which is a rare condition with just a few reports about it in the literature. This finding is harmless and requires no treatment.

[Dynamic Scheimpflug Analyzer (Corvis ST) for measurement of corneal biomechanical parameters : A praxis-related overview]. / Dynamischer Scheimpflug-Analyzer (Corvis ST) zur Bestimmung kornealer biomechanischer Parameter : Ein praxisbezogener Überblick.

BACKGROUND: Topographic and tomographic parameters alone are often not sufficient for early detection of corneal changes. Pathological alterations in the microstructure of the cornea occur before changes in topography and tomography can be detected. Biomechanical parameters show a strong correlation with microscopic structural changes. OBJECTIVE: The aim of the study was to gain information about the microscopic structure and consistency of the cornea by measuring biomechanical parameters. MATERIALS AND METHODS: The deformation behavior of the cornea was analyzed with the Dynamic Scheimpflug Analyzer (Corvis ST; OCULUS, Wetzlar, Germany). Deformation parameters and biomechanical indices were derived from the deformation response of the cornea. RESULTS: Deformation parameters and indices in keratoconus patients differ significantly from healthy subjects. Alterations of the cornea can be detected before topographic and tomographic changes occur. The repeatability and reproducibility of relevant deformation parameters is good to very good. In glaucoma patients a modified deformation behavior of the cornea can be observed, which might be related to structural changes. CONCLUSION: The Corvis ST allows a reliable characterization of the tissue structure and consistency of the cornea.

[Initial Clinical Experiences Using Ocriplasmin for the Treatment of Vitreomacular Traction with or without a Macular Hole]. / Stellenwert von Ocriplasmin bei der Therapie der vitreomakulären Traktion mit und ohne Makulaforamen ­ erste klinische Erfahrungen.

PURPOSE: In vitreomacular traction (VMT), there is abnormal adhesion between the vitreous cortex and the retina, especially in the fovea. Symptoms of VMT include metamorphopsia and a decrease in visual acuity. Since 2013, ocriplasmin (Jetrea®) has been approved for treatment of symptomatic vitreomacular traction with or without macular holes (≤ 400 µm). METHODS: We retrospectively examined twenty-three eyes of twenty-one patients who underwent intravitreal ocriplasmin treatment for symptomatic vitreomacular traction with or without macular holes. Best corrected visual acuity and central retinal thickness (CRT) were measured in advance and after ocriplasmin treatment. The numbers of resolved vitreomacular traction and closed macular holes were documented. RESULTS: Vitreomacular traction was resolved in eight of twenty-three eyes (34.8 %); in fifteen eyes (65.2 %) it was persistent and two of four macular holes were found closed. The average best corrected visual acuity was 0.39 ± 0.25 logMAR at baseline and 0.41 ± 0.24 logMAR at the first follow-up visit after injection (p = 0.613). The average CRT was 453.3 ± 172.7 µm at baseline, with a slight decrease to 412.0 ± 212 µm (p = 0.124). CONCLUSION: Intravitreal injection of ocriplasmin appears is an experimental therapy in patients with symptomatic vitreomacular traction. Patient selection seems to be critically important for the therapeutic outcome, whereas greater age, specific VMT morphology and missing chromatopsia seem to be negative predictors.

[Methotrexate in Atypical Non-Arteritic Ischemic Optic Neuropathy]. / Methotrexat bei atypischer nicht arteriitischer anteriorer ischämischer Optikusneuropathie.

Background: Optic nerve disease can occur from a variety of different causes, with vascular, inflammatory or toxic pathologies. In such cases, it is hardly possible to clarify the aetiology. These diseases of the optic nerve are usually accompanied by progressive loss of visual field and visual impairment. Patient: We report a case of a 74-year-old woman complaining of loss of visual acuity, visual and blurred vision in the left eye in 2010. We made the diagnosis of non-arteritic ischemic optic neuropathy (NAION). With steroid therapy, there was an improvement in both visual acuity and visual field defects. But if an attempt was made to reduce steroids, her condition progressed. Except for a very small optic disk and arterial hypotension, there were no typical risk factors for NAION. We started treatment with methotrexate (MTX), with a starting dose of 10 mg per week, and observed the patient over two years. Results: Using MTX therapy, the swelling of the optic nerve head and visual field loss were reversible, so we increased the dose of MTX up to 15 mg/week. Steroid therapy could be stopped and the patient's visual acuity and visual field have now been stable for two years. There was no visible pallor in the optic nerve head, as normally occurs after AION, so we considered different underlying pathologies, including autoimmune disease. There were no adverse events with MTX therapy. Conclusion: If the course of the disease is atypical, the pathology may include an autoimmune component. Immunosuppressive MTX therapy may be started in order to avoid long-term steroid use. It may then be possible to maintain a stable visual field and prevent remitting episodes.

[Effectiveness of Intravitreal Aflibercept Injections in Patients who had Received 10 and More Ranibizumab Injections in Advance]. / Wirksamkeit von Aflibercept bei Patienten mit mehr als 10 vorangegangenen intravitrealen Ranibizumab-Injektionen.

BACKGROUND: Since 2007, the standard treatment for age related macular degeneration has been intravitreal injection of ranibizumab. However, despite continuous treatment, some patients fail to achieve remission or stabilisation of the disease. Since 2012, the recombinant fusion protein aflibercept has been available as an alternative treatment. In this study, we investigated whether patients who appear to be resistant to ranibizumab would benefit from treatment with aflibercept. METHODOLOGY: This retrospective study covered 83 eyes of 81 patients, for whom treatment switch from ranibizumab to aflibercept was indicated. Inclusion criteria were an age ≥ 50 years and at least 10 ranibizumab injections before a switch to aflibercept. Patients with severely impaired visual acuity were excluded. Primary outcomes were improvement or loss of visual acuity (VA) and evaluation of central macular thickness (CMT) via SD-OCT. Secondary endpoints were percentage of eyes without activity of the choroidal neovascular membrane after aflibercept injections and loss or gain of letters on the visual chart. Statistical analysis was performed using SPSS. RESULTS: VA was 0.83 ± 0.34 logMAR before the first aflibercept injection, with a slight but not statistically significant improvement up to 0.79 ± 0.33 logMAR after the third aflibercept injection (p = 0.205). On the other hand, there was a clear reduction of CMT in OCT, from 451.4 ± 263.0 to 288.2 ± 128.2 µm (p = 0.0001). Overall, 73 % of eyes exhibited better or stable VA and 27 % of eyes lost VA. Interestingly, eyes with worse initial VA gained greater benefit from the switch to aflibercept (p = 0.001). CONCLUSION: A switch to aflibercept may lead to stabilisation of choroidal neovascularisation and thus stabilise the visual acuity for patients who appear to be no longer responsive to treatment with ranibizumab.

[Corneal collagen cross-linking with riboflavin and ultraviolet-A light in progressive keratoconus. Results after 10-year follow-up]. / Hornhautkollagenvernetzung mit Riboflavin und UVA-Licht bei Patienten mit progressivem Keratokonus : 10-Jahres-Ergebnisse.

PURPOSE: Riboflavin and ultraviolet-A induced cross-linking (CXL) is a promising therapeutic option to halt the progression of keratoconus. The aim of the study was to prove a long-term stabilizing effect of riboflavin and ultraviolet-A induced collagen CXL in young and otherwise healthy patients with progressive keratoconus and a corneal thickness of at least 400 µm on average 10 years after treatment. METHODS: Corneal CXL was performed after removing epithelial tissue by instilling riboflavin 0.1% solution for 30 min before and during 30 min of ultraviolet-A irradiation (370 nm, 3 mW/cm(2)). This long-term retrospective study included 30 eyes of 20 patients with progressive keratoconus. Preoperative and postoperative examinations on average 10 years after treatment included best corrected visual acuity (BCVA), corneal topography (keratometry values KMAX, KMIN and KApex), corneal thickness (CT) and if available endothelial cell density. RESULTS: The mean preoperative age was 28 ± 7 years (range 14-42 years), 4 patients were female (7 eyes) and 16 patients (23 eyes) were male. Preoperatively, the mean K-value on the apex of keratoconus was 62 ± 13.2 dpt which showed a statistically significant reduction after 10 years to 55 ± 8.1 dpt (p = 0.001). The mean KMAX (53 ± 8.2 versus 49 ± 6.6 dpt) and KMIN values (48 ± 5.5 vs. 45 ± 5.1 dpt) also showed a statistically significant decrease (p = 0.001). In comparison BCVA also showed a statistically significant preoperative and postoperative difference (p = 0.005). There was a significant improvement of BCVA by a mean of - 0.13 ± 0.25 logMAR. The mean change in corneal thickness at the 10-year follow up was 46 µm (p = 0.001). Bias possibly occurred because of a change of the measurement method from ultrasound pachymetry to optical pachymetry with Oculus Pentacam®. Neither corneal endothelium nor deeper structures suffered any damage. Only two patients had continuous progression of keratoconus and needed a reapplication of CXL. CONCLUSION: The results of this study indicate that riboflavin and ultraviolet-A induced corneal CXL is a promising therapeutic option for progressing keratoconus to obtain long-term stabilization. There was a sustained improvement of all K-values and BCVA 10 years after treatment and CXL is minimally invasive and easy to handle. Side effects, such as endothelial damage did not occur.

[Ankyloblepharon filiforme adnatum]. / Ankyloblepharon filiforme adnatum.

The ankyloblepharon filiforme adnatum is a congenital eyelid anomaly in which the development of the eyelids is completed but the eyelids are not completely separated at birth. The abnormality can occur as an isolated anomaly, together with other eye diseases or in the context of systemic syndromes. In this case report the current classification and essential diagnostics of AFA will be reviewed.

[Sebaceous gland tumor with a rare gene mutation within a tumor syndrome: Muir-Torre syndrome]. / Talgdrüsenkarzinom mit seltener Genmutation im Rahmen eines Tumorsyndroms: Muir-Torre-Syndrom.

Muir-Torre syndrome is a rare autosomal dominant subtype of hereditary nonpolyposis colorectal carcinoma and is characterized by the simultaneous occurrence of sebaceous gland neoplasms with visceral and urogenital malignancies. This article describes the case of a 72-year-old patient who was referred to our clinic for removal of an upper eyelid tumor, showing the course from the clinical findings to the rare diagnosis of Muir-Torre syndrome.

[Therapy-resistant swelling of the upper eyelid in childhood]. / Therapieresistente Oberlidschwellung im Kindesalter.

HISTORY: Swelling of the upper eyelid in childhood is caused by a variety of diseases and is very often generated by inflammation but orbital tumors should always be considered in the differential diagnostics. METHODS: We report about a 4-year-old girl with a drug-resistant swelling of the upper eyelid and ptosis of the right eye. This case report demonstrates the route from initial clinical examination to diagnosis and additionally reviews the current status of therapeutic options. RESULTS: After magnetic resonance imaging (MRI) and diagnostic excision, Langerhans cell histiocytosis (LCH) could be histologically proven. Visual acuity and levator muscle function improved from 0.5 to 1.25 and from 2 mm to 12 mm, respectively, by amblyopic prophylaxis and immunosuppressive therapy. CONCLUSIONS: Persistent and drug-resistant swelling of the upper eyelid in childhood is also strongly suspicious for tumors. The suspicion of rare orbital tumors in children can be frequently substantiated by MRI. Biopsy and histological diagnosis are essential to plan adequate treatment and to estimate the prognosis. Particularly in Langerhans cell histiocytosis the methods of choice for over 10 years are specific immunochemical procedures (detection of protein s100 and CD1a).

[Retinal hemorrhages after Ahmed glaucoma valve implantation]. / Retinale Blutungen nach Ahmed-Drainage-Implantation.

A 31-year-old male patient developed uncontrolled elevation of intraocular pressure (IOP) under maximum tolerated therapy after severe blunt trauma to the right eye. For IOP control an Ahmed glaucoma valve implantation was necessary. On the first postoperative day the patient presented with retinal hemorrhages typical for decompression retinopathy. After a period of 6 months the hemorrhages had almost resolved and visual acuity was unaffected. The clinical picture of the case and possible mechanisms of this rare entity, which usually appears after incisional glaucoma surgery, are presented.

[Effectivity of an occlusion-supporting PC-based visual training programme by horizontal drifting sinus gratings in children with amblyopia]. / Webbasierte Stimulationstherapie bei Kindern mit unbehandelter Amblyopie.

BACKGROUND: The studies of Kämpf et al. suggested an efficiency of a computer-based stimulation therapy by drifting sinus gratings in patients with anisometropic and/or strabismic amblyopia but provided no clear evidence. This is the first trial with amblyopic patients without previous treatment at the beginning of amblyopia therapy. METHODS: A prospective, randomised, single-blinded, placebo-controlled study of n = 15 patients with anisometropic and/or strabismic amblyopia without previous treatment was performed. Age of the patients was between 4 and 10 years, mean 6.3 years (± 2.0), all after full correction of refraction errors and refractive adaptation. Stimulation therapy was performed 5 times a week over 4 weeks, respectively 2 × 20 min, a drifting sinus grating of constant spatial and temporal frequency was combined with computer games (n = 8). Control group had only computer games with a neutral background (n = 7). In both groups patching was only done in stimulation times. RESULTS: Stimulation and control group did not differ due to age, gender, and cause of amblyopie, baseline visual acuity, and time of wearing glasses. There was no significant difference in the development of visual acuity over the stimulation period between stimulation and control groups. CONCLUSIONS: Stimulation therapy with drifting sinus gratings did not improve the development of visual acuity in the first phase of amblyopia treatment combined with minimal occlusion therapy. Accordingly, the stimulation therapy is not adequate to replace sufficient occlusion therapy. Whether this therapy could support patching therapy and improve acuity development in later therapy phases cannot be assumed from this trial.

[Measurement of retinal thickness with the Heidelberg retina tomograph for patients with macular edema and healthy individuals]. / Netzhautdickenmessung mit dem Heidelberg Retina Tomograph bei Patienten mit Makulaödem und bei Gesunden.

BACKGROUND: This study was carried out to test the reliability of a defined cut-off value for retinal thickness with estimation of the sensitivity, specificity and formation of an edema index in comparison to retinal thickness. MATERIALS AND METHODS: This was a single center prospective clinical non-blinded study of 100 eyes, including 22 eyes with central vein or branch vein occlusions, 20 eyes with diabetic macular edema, 6 eyes with postoperative macular edema, 2 eyes with uveitis and 50 healthy eyes. Detection of macular edema was carried out by third generation optical coherence tomography. Using the latest version of the Heidelberg retina tomograph (HRT 3) series of five images were produced and evaluated. The 9-zone circle of the HRT was used as the analysis contour. RESULTS: The reliability of measuring retinal thickness with the HRT in the subjects showed an intraclass correlation between 0.248 and 0.740 and patients with macular edema showed values between 0.515 and 0.949. The reliability of the edema index with the HRT in the subjects showed an intraclass correlation between 0.461 and 0.826 and patients with macular edema showed values between 0.383 and 0.826. The calculated cut-off values were between 285 µm and 360 µm. The corresponding sensitivity values were between 74.7% and 95.9% with a corresponding specificity of 74.7-90.2%. There was also a highly significant correlation between the edema index and retinal thickness (p < 0.001). CONCLUSIONS: The retina module of the latest generation HRT is capable of reproducible measurement of the retinal thickness in micrometers. The defined cut-off values correspond to expectations and can be used in this form in the clinical practice.

[Corneal cross-linking with hypo-osmolar riboflavin solution for keratoconus with thin corneas]. / Hornhautvernetzung mit hypoosmolarer Riboflavin-Lösung beim Keratokonus mit dünner Hornhaut.

BACKGROUND: The aim of this study was to evaluate the 1-year results of 32 keratoconic eyes with thin corneas which were treated by hypo-osmolar riboflavin solution and ultraviolet A (UVA) collagen cross-linking (CXL). PATIENTS AND METHODS: Patients with progressive keratoconus and a corneal thickness (CT) less than 400 µm (without epithelium) were included in this study. The CT was measured with an ultrasound device (Tomey SP-3000, Nishi-ku, Nagoya, Japan). An increase in the maximum topographic K-value at the apex of keratoconus and a reduction in corneal thickness with or without changes in visual acuity (VA) within the last year were considered to be progression. A total of 32 eyes with an additional follow-up within 1 year were evaluated before and after the procedure. Examinations consisted of an evaluation of VA, corneal topography, slit-lamp microscopy and corneal thickness measurements. RESULTS: Preoperatively the mean corneal thickness (with epithelium) was 382.3±41.9 µm and after removal of the epithelium the thickness of the cornea was reduced to 337.0±51.9 µm. After the application of hypo-osmolar riboflavin solution the mean value increased to 451.8±46.7 µm. Preoperatively the mean K-value of the apex of the keratoconus was 65.6±11.2 dopters, and 1 year after treatment this value remained relatively unchanged at 64.9±11.0 diopters (P=0.839). Mean VA at the time of the treatment was 0.63±0.37 logMAR and 1 year after the treatment this value was not statistically different (0.59±0.42 logMAR; P=0.662). In the last follow-up examination 1 year after the procedure all corneas were transparent without any scarring lesions in the stroma. CONCLUSIONS: The results of this study using hypo-osmolar riboflavin solution in a cross-linking procedure for thin corneas showed a stability of keratoconus 1 year after CXL. Application of the hypo-osmolar riboflavin solution prevented cross-linked corneas from developing stromal scars.

[Gingival hyperplasia and visual reduction]. / Zahnfleischschwellung und Visusreduktion.

This case report describes the unilateral acute reduction of vision in the right eye of a 48-year-old woman. The patient was otherwise healthy but 2 days previously had suffered from dizziness and blurred vision. Secondary to this, the patient had already been under dental treatment for 1 week due to gingival swelling. At the first examination a macular branch retinal vein occlusion and Roth spots were found in the right eye by indirect ophthalmoscopy. The immediate diagnostic procedure identified aute amyeloid leukemia (AML) as the cause of the vascular pathology. The AML can be manifested in different ways and the retina is involved in approximately 50% of cases. Due to a secondary hyperviscosity syndrome, which is found in approx. 20% of acute leukaemias, symptomatic central vein occlusion or macular branch vein occlusion can occur. Ophthalmic symptoms can be the first and only signs to be detected. Therefore, ophthalmologists should also consider a systemic disease and initiate a clarification. A differential blood count is indispensable. The results usually improve by a rapidly arranged and suitable therapy. Ophthalmological follow-up examinations are imperative as an initiated chemotherapy can also produce ophthalmological side-effects.

[Maculopathy with subretinal yellow deposits]. / Makulopathie mit subretinalen, gelblichen Ablagerungen.

We present the case of a 52-year-old female patient who presented with bilateral loss of vision over the course of several years. Funduscopy revealed multiple drusen in a "honeycomb"-like configuration at the entire posterior pole and in the peripapillary region. Autofluorescence and fluorescence angiography (FLA) showed multiple hyperfluorescent defects which show no leakage due to staining of the drusen-like lesions. Optical coherence tomography (OCT) revealed a marked irregularity of the photoreceptor-retinal pigment epithelium complex. Electroretinography (ERG) was without pathological findings, while the electrooculography (EOG) was abnormal, reflecting a functional disturbance of the retinal pigment epithelium. In consideration of all clinical findings, our patient suffered from Doyne honeycomb retinal dystrophy (DHRD) which is a rare autosomal dominant inherited retinal disease with full penetrance. Patients with DHRD are usually asymptomatic until the age of 30-40 years. In the later stages of this disease, central vision deteriorates as a result of geographic atrophy or choroidal neovascularization.

[Siderosis bulbi after injury by an intraocular metal foreign body]. / Siderosis bulbi nach intraokularem Metallfremdkörper.

We report the case of a 42-year-old patient who presented with unilateral loss of vision in the left eye. The clinical examination revealed retinal detachment and a low intraocular pressure was found in the left eye. Except for an extinct electroretinogram (ERG) and a siderosis bulbi in the left eye no signs of an intraocular body were detectable, either in the ultrasound B-scan or in the clinical examination. Pars plana vitrectomy with silicon oil tamponade was performed and revealed an iron-containing body next to the fovea which was removed without any complications. Despite an initially easily visible retinal detachment, a newly acquired siderosis bulbi in combination with ocular trauma in the clinical history should raise the suspicion of a residual intraocular iron foreign body, until this can be disproven.