Internal Limiting Membrane Flap Techniques for the Repair of Large Macular Holes: a Short-Term Follow-up of Anatomical and Functional Outcomes.

Background To evaluate the technique of inverted internal limiting membrane (ILM) flaps for the management of large macular holes and autologous ILM free flaps for non-closing macular holes. Patients and methods All macular holes were treated with pars plana vitrectomy and dual blue assisted ILM flap technique. The inverted ILM flap was created as a primary procedure for large macular holes (diameter > 400 µm). On the other hand, the free ILM flap technique was used as a secondary procedure for non-closing macular holes after failed initial standard procedure. SD-OCT images were taken to assess the anatomical outcome of surgery, while best corrected visual acuity (BCVA) was used to evaluate the functional outcome during a 2-month follow-up. Results All patients underwent successful planned manipulation of the ILM flap. In seven patients/eyes, an inverted ILM flap was created, in three patients/eyes a free ILM flap translocation was performed. All patients achieved complete anatomical closure. Partial microstructural reconstruction, demonstrated on SD-OCT as restoration of the external limiting membrane and the ellipsoid zone, was observed in some cases as early as one month after surgery. Functionally, in comparison to baseline, most of the patients showed improvements in BCVA of 1 to 2 lines at the first postoperative follow-up visit. Conclusions Inverted ILM flaps for large macular holes and free flaps for non-closing macular holes appear to be a safe and effective approach, with favourable short-term anatomical and functional results.

Prominent Optic Disc Featured in Inherited Retinopathy.

Background We investigated the relationship between prominent optic disc (POD) and inherited retinal dystrophy (IRD). Patients and Methods A cross-sectional consecutive study was performed in 10 children and 11 adults of 7 non-related families. We performed clinical phenotyping, including a detailed examination, fundus autofluorescence, and colour fundus and OCT imaging. Genetic testing was subsequently performed for all family members presenting retinal pathology. Results In 4 members of a 3-generation family, hyperfluorescent deposits on the surface of POD were related to a p.(L224M) heterozygous mutation in BEST1. In the second family, one member presented deposits located on the surface on hyperaemic OD and a compound p.(R141H);(A195V) mutation in BEST1. In the third family, POD was observed in father and child with early onset cone-rod dystrophy and a novel autosomal recessive p.(W31*) homozygous mutation in ABCA4. In the fourth family, POD with "mulberry-like" deposits and attenuated vessels were observed in a 7-year old girl, with a mutation in USH1A, and with early onset rod-cone dystrophy, associated with hearing loss. In the fifth family, blurry OD with tortuous vessels was observed in 4 consanguineous female carriers and a hemizygous boy with a p.(R200H) mutation in the X-linked retinoschisis RS1. In the sixth family, a mother and her son were both affected with POD and attenuated peripapillary vessels, and presented with a p.(Y836C) heterozygous mutation in TOPORS, thus confirming autosomal dominant RP. In the seventh family, in 3 family members with POD, compound p.(L541P;A1038 V);(G1961E) mutations in ABCA4 confirmed the diagnosis of Stargardt disease. Conclusions A variety of OD findings are found in a genetically heterogeneous group of IRDs. In the presence of POD, an inherited progressive photoreceptor disease should be ruled out.

The association between retinal nerve fibre layer thickness and N-acetyl aspartate levels in multiple sclerosis brain normal-appearing white matter: a longitudinal study using magnetic resonance spectroscopy and optical coherence tomography.

BACKGROUND AND PURPOSE: N-acetyl aspartate (NAA) assessed using proton magnetic resonance spectroscopy (1 H MRS) has a high pathological specificity for axonal density. Retinal nerve fibre layer thickness (RNFLT) measured by using optical coherence tomography is increasingly used as a surrogate marker of neurodegeneration in multiple sclerosis (MS). Our aim was to investigate the relation between RNFLT and NAA/creatine in brain normal-appearing white matter (NAWM), their dynamics over time and the association with clinical outcome measures in relapsing MS. T2 WM lesions served as control tissue. METHODS: Forty-three MS patients underwent standardized neurological examination including the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC) score, optical coherence tomography and magnetic resonance imaging including 1 H MRS at baseline and after 1 year. RESULTS: At baseline, NAA/creatine level was lower in T2 WM lesions than in NAWM (1.64 ± 0.16 vs. 1.88 ± 0.24, P < 0.001). Lowest levels were found in secondary progressive MS (SPMS). Mean RNFLT was higher in clinically isolated syndrome than in the combined group of relapsing-remitting MS and SPMS (99.8 ± 12.3 µm vs. 92.4 ± 12.8 µm, P = 0.038). In all patients, mean RNFLT decreased by 1.4% during follow-up. At baseline, MSFC z-scores correlated with NAA/creatine levels both in NAWM (r = 0.42; P = 0.008) and T2 WM lesions (r = 0.52, P = 0.004). NAWM NAA/creatine variation correlated with the RNFLT change over 1 year (ρ = 0.43, P = 0.046). CONCLUSIONS: N-acetyl aspartate/creatine level reduction correlated with RNFLT thinning over 1 year in an EDSS stable MS cohort suggesting that these techniques might be sensitive to detect subclinical disease progression.

[Disease perception in patients with wet age-related macular degeneration]. / Krankheitswahrnehmung bei Patienten mit einer feuchten altersabhängigen Makuladegeneration.

BACKGROUND: The disease perception of the patients treated with intravitreal injections of anti-vascular endothelial growth factor due to wet age-related macular degeneration was investigated. PATIENTS AND METHODS: 177 questionnaires focusing on the development of the perceived visual acuity and the quality of life were evaluated. The subgroup 1 included 125 patients (70.6%) with a unilateral wet age-related macular degeneration. The subgroup 2 included 52 patients (29.4%) with a bilateral wet age-related macular degeneration. RESULTS: Patients would almost always recommend the therapy to a friend (97.2%). The critical remarks are related to the uncertain course of the disease (22.8%) and the uncertain duration of the treatment (19%). There was a discrepancy between the measured visual outcome and the perceived one in 5.6% in the subgroup 1, and in 38.5% in the subgroup 2. This difference was statistically significant (chi-square test with p<0.01). CONCLUSIONS: The treatment of wet age-related macular degeneration with intravitreal injections of anti-vascular endothelial growth factor is judged positively. Binocular affected patients have a higher disease perception and therefore a poorer self-assessment of their visual acuity and their quality of life compared with monocular affected patients.

[The role of chronic or transient hypoxia on the retinal nerve fiber layers]. / Die Rolle einer chronischen oder einer transienten Hypoxie auf die retinalen Nervenfaserschichten.

BACKGROUND: In a clinical study, the role of chronic hypoxia in patients with chronic obstructive pulmonary disease or the role of transient hypoxia in patients with obstructive sleep apnea syndrome were examined for the peripapillary retinal nerve fiber layers. PATIENTS AND METHODS: 10 patients with chronic obstructive pulmonary disease GOLD stages 3 or 4 (4 men and 6 women, age 47 to 71 years, mean 60.6 years) and 10 patients with obstructive sleep apnea syndrome with an apnea-hypopnea index of 15 or more (8 men and 2 women, age 39 to 76 years, mean 60.7 years) were included in the study. The thickness of the retinal nerve fiber layers was measured with an optical coherence tomography. RESULTS: In the group with chronic obstructive pulmonary disease and in the group with obstructive sleep apnea syndrome, the measurements of the retinal nerve fiber layers were in normal range. CONCLUSIONS: By using optical coherence tomography, no lesions to the retinal nerve fiber layers were detectable in patients with chronic or transient hypoxia. The findings of the study could be limited by the too short duration of the disease and/or to the too small number of patients.

Retinal vessel oxygen saturation in patients suffering from inherited diseases of the retina.

PURPOSE: The aim of this study was to evaluate the oxygen saturation in patients with inherited diseases of the retina. METHODS: Fundus oximetry images were taken using a retinal vessel analyser (IMEDOS Systems UG, Jena, Germany). Retinal vessel oximetry was performed in 53 eyes of 27 patients suffering from inherited retinal diseases and compared to 22 eyes of 11 healthy controls. The oxygen saturation in all four major retinal arterioles (A-SO2) and venules (V-SO2) were measured and their difference (A-V SO2) was calculated. The data were compared within groups and to controls. RESULTS: Based on V-SO2 values, the rod-cone dystrophy group (66.46%; SD, ± 5.09) could well be differentiated from controls 54.02% (SD, ± 3.04), from cone-rod dystrophies 57.56% (SD, ± 5.66), as well as from inherited maculopathies 58.42% (SD, ± 4.74). The mean A-SO2 in the rod-cone dystrophy group was increased to 98.96% (SD, ± 6.06, p<0.014), while in the cone-rod group and in the maculopathy group it was 92.75% (SD, ± 3.75), respectively 94.44% (SD ± 4.85), closer to the normal values (92.68%; SD, ± 3.53, p>0.05). The A-V SO2 difference, as an indirect indicator for retinal oxygen use, was reduced in the rod-cone patients, however only when the controls were taken into account (p=0.01). CONCLUSION: This is to our knowledge the first study which proposes the retinal vessel oximetry to be a sensitive measure for differentiating rod-cone dystrophy patients not only from controls, but also from patients with other inherited retinal dystrophies.

[Bevacizumab and Ranibizumab for macular edema due to retinal vein occlusions]. / Bevacizumab und Ranibizumab bei Makulaödem bei retinalen Venenverschlüssen.

BACKGROUND: The effect of Bevacizumab (BE) (Avastin®) or Ranibizumab (RA) (Lucentis®) on the visual acuity (VA) and on the central foveal thickness (CFT) was evaluated in macular edema due to retinal vein occlusion. PATIENTS AND METHODS: Eyes with a macular edema due to a central retinal vein occlusion or to a branch retinal vein occlusion were considered if at least 3 intravitreal injections of Bevacizumab (1.25 mg) or Ranibizumab (0.5 mg) had been performed. The visual acuity with ETDRS and the central foveal thickness with spectral optical coherence tomography (OCT) were measured. The 3-months follow-up and, if further injections were necessary, the 6-months follow-up were evaluated. RESULTS: After 3 months a significant improvement of the visual acuity was measured in both groups (p < 0.001) while during the same period the mean central foveal thickness diminished significantly (p < 0.001). At the 3-months follow-up there were no significant differences between the two groups for the mean visual acuity and for the mean central foveal thickness. The treatment was continued in 36 eyes and the visual acuity and the central foveal thickness were compared between the 3-months and the 6-months follow-up. No further improvements of the visual acuity or of the central foveal thickness were measured in both groups. A relapse of the macular edema was diagnosed in 30 eyes without a significant difference in the Bevacizumab group compared to the Ranibizumab group. CONCLUSION: Intravitreal injections of Bevacizumab and Ranibizumab improved the visual acuity and the central foveal thickness in macular edema due to retinal vein occlusion at 3 months. A further improvement was not measured if the treatment was prolonged to 6 months. There were no significant differences measured between Bevacizumab and Ranibizumab. The ratio of relapses is important to note.

[Dexamethason implant in the treatment of macular edema in retinal vein occlusion and intraocular inflammatory disease]. / Dexamethasonimplantat zur Behandlung des Makulaödems bei retinalen venösen Gefäßverschlüssen und entzündlichen Augenerkrankungen.

BACKGROUND: The efficacy of a single dose of Ozurdex® was evaluated over a 6-month period in eyes with macular edema due to retinal vein occlusion and intraocular inflammatory disease. HISTORY AND SIGNS: 20 eyes of 20 consecutive patients with macular edema received a single injection of Ozurdex® (intravitreal dexamethasone implant 0.7 mg). Patients with branch retinal vein occlusion (n = 11), central retinal vein occlusion (n = 6), non-infectious posterior uveitis (n = 1) and Irvine-Gass Syndrome (n = 2) were included. In 10 patients Ozurdex® was used as the first treatment, 10 patients had undergone previous treatments for macular edema. The mean duration from the symptoms to the initiation of the treatment was 14.2 (1-60) months. The follow-up measurements were performed 1, 3 and 6 months after treatment. The main interest of the study was the visual and structural development over the duration of 6 months after a single dose of Ozurdex® with outcome measures including changes in best-corrected visual acuity and central retinal thickness. THERAPY AND OUTCOME: At baseline, the mean best-corrected visual acuity of all patients was 50 (± 16) ETDRS letters and the mean central retinal thickness was 632 (± 168.3) microns. Mean follow-up time was 3.4 (± 1.5) months and 7 patients dropped out during the follow-up period (4 patients after 3 months, additional 3 patients after 6 months). One month after treatment, 14 out of 20 patients (70%) showed a complete regression of macular edema, and in 6 cases (30%) it was partially recurrent. The mean best-corrected visual acuity improved to 56 (± 20.8) ETDRS. Central retinal thickness showed a mean decrease to 278 (± 84.9) microns. 6 months after treatment, recurrence was observed in 9 cases out of the remaining 13 patients (69.2%). In 3 cases, macular edema persisted (23.1%) and in one case (7.7%) the macula remained dry. The mean best-corrected visual acuity was 55 (± 13.9) ETDRS letters. The mean central retinal thickness decreased to 603 (± 174.6) microns. CONCLUSIONS: Ozurdex® showed a good effect in the treatment of macular edema one month after its application, namely a temporary decrease in central retinal thickness and a corresponding increase in best-corrected visual acuity. 6 months after treatment, the recurrence rate was high, and only one person with a branch retinal vein occlusion remained relapse-free over the entire follow-up. Based on our data, the patients should be checked at the latest after 3 months and then monthly in order to detect relapse in time and to initiate another treatment if needed.

Photodynamic therapy in the treatment of persistent central serous chorioretinopathy: a two-year follow-up.

BACKGROUND: The aim of this study was to assess during a follow-up period of two years the efficacy and safety of photodynamic therapy (PDT) in central serous chorioretinopathy (CSC) showing no spontaneous resolution four months after the onset of the symptoms. PATIENTS AND METHODS: We present a prospective interventional non-comparative case series. The diagnosis of CSC was confirmed by fluorescein angiography (FA), and optical coherence tomography (OCT) in 46 eyes of 42 consecutive patients. PDT was performed according to the protocol used for treating choroidal neovascularization in age-related macular degeneration. The primary end point was to assess the anatomic re-attachment of the retina. The secondary end point was to record the visual function. A paired t-test and a linear regression and correlation test were used for the statistics. RESULTS: The leakage in FA and the detachment of the neurosensory retina in OCT were no longer present in 42 eyes six weeks after PDT and in the remaining four eyes three months after PDT. At the end of the follow-up, the best-corrected visual acuity measured with an ETDRS chart improved in 36 eyes, and remained stable in 10 eyes (mean improvement, 10.2 letters; p < 0.001). Two cases of recurrence were diagnosed. No treatment-related complications were noticed. CONCLUSIONS: PDT could be an effective and durable option for treating patients with persistent CSC.

New guidelines in the treatment of persistent central serous chorioretinopathy: PDT with half-dose verteporfin.

BACKGROUND: In persistent central serous chorioretinopathy (CSC) resolution of detachment can be achieved by photodynamic therapy. Our objective was to evaluate the efficacy of half-dose verteporfin compared to full-dose verteporfin. PATIENTS AND METHODS: In 2009 the standard PDT regimen for CSC in our clinic was changed from full-dose to half-dose verteporfin. After a retrospective analysis 11 cases of half-dose PDT with documented course in 11 patients are presented. A comparison was performed with a control group of 11 consecutive patients with documented course who had received full-dose PDT before 2009. RESULTS: Prior to PDT there were no statistically significant differences between the groups concerning age, central foveal thickness, thickness of detachment, BCVA (EDTRS) and size of spot. 6 weeks after PDT a significant reduction of foveal thickness and detachment was detected in both groups, as well as a significant increase in BCVA. No statistically significant differences in outcome could be found between the two groups (Mann-Whitney U-test, p < 0.05). CONCLUSIONS: PDT with half-dose verteporfin seems to be an effective and safe treatment for persistent CSC. Our data showed comparable results after half-dose and after full-dose PDT.

[Heavy tamponade in complicated inferior retinal detachment]. / Schwere Tamponade bei komplizierten inferioren Netzhautablösungen.

BACKGROUND: Retinal detachment with inferior proliferative vitreoretinopathy is a difficult to treat problem. The aim of our study was to assess the safety and efficacy of Densiron in the clinical management of complicated retinal detachment. HISTORY AND SIGNS: 6 eyes of 6 consecutive patients presenting with a retinal detachment with inferior proliferative vitreoretinopathy grade 3 were treated with pars plana vitrectomy and injection of Densiron. The mean age of the patients was 61 years. 3 patients had a previous unsuccessful vitreoretinal surgery and 3 patients had Densiron as a first procedure. The extent of detachment was at least 2 or more quadrants with macular involvement in 3 cases. Preoperatively the mean visual acuity was 29.2 letters with ETDRS. THERAPY AND OUTCOME: Densiron was removed after an average of 58 days. 5 patients achieved retinal re-attachment without further tamponade, and 1 patient after additional injection of conventional silicon oil. 4 - 6 weeks after removal of Densiron the mean visual acuity was 50.2 letters with ETDRS. The most common complication was an elevated intraocular pressure during endotamponade, which resolved following removal of the agent. CONCLUSIONS: Densiron improves inferior tamponade, and in clinical practice may be considered to increase the anatomic success rate in selected cases of complicated retinal detachment with inferior proliferative vitreoretinopathy.

[Photodynamic therapy in "Secondary Sick RPE Syndrome" after repeated intravitreal injections of VEGF inhibitors in patients with wet age-related macular degeneration]. / Fotodynamische Therapie bei "Secondary Sick RPE Syndrome" nach wiederholten intravitrealen Injektionen von VEGF-Inhibitoren bei Patienten mit feuchter altersabhängiger Makuladegeneration.

BACKGROUND: After repeated injections of VEGF inhibitors for wet AMD some patients show therapy-resistant isolated subretinal fluid (here named secondary sick RPE syndrome). The efficacy of photodynamic therapy was examined in these cases. PATIENTS AND METHODS: A group of in total 18 patients with wet AMD (14 eyes with occult and 4 with minimal classic CNV) showed therapy-resistant isolated subretinal fluid after repeated intravitreal injections of VEGF inhibitors (bevacizumab or ranibizumab). These eyes were treated with photodynamic therapy with verteporfin. After PDT the need for further intravitreal injections of VEGF inhibitors and visual acuity was examined. RESULTS: After a mean number of 7.1 injections of VEGF inhibitors (bevacizumab or ranibizumab), in 14 patients one PDT, in 4 patients two PDT were performed. Twelve of 18 patients showed complete resorption of subretinal fluid and needed no further intravitreal injections during a mean of 11.6 months (4 - 26) after PDT. Six patients needed a mean of 4.3 additional injections. Twelve of 18 patients showed stable visual acuity (± 5 letters ETDRS), 6 improved more than 5 letters while none of them showed visual loss. CONCLUSIONS: In patients with wet AMD and isolated subretinal fluid after repeated injections of bevacizumab or ranibizumab photodynamic therapy could be an option to reduce the number of further injections and to stabilise visual acuity.

The treatment of choroidal neovascularizations in age-related macular degeneration using either Avastin or Lucentis.

BACKGROUND: Either Avastin or Lucentis was used in our clinic to treat choroidal neovascularizations in age-related macular degeneration. The number of injections necessary for drying the macular findings was especially assessed. PATIENTS AND METHODS: From April 2006 to August 2008 324 eyes were treated with Avastin, and from January 2007 to August 2008 348 eyes were treated with Lucentis. The intravitreal injections with Avastin (1.25 mg in 0.05 mL) were performed every six weeks, and with Lucentis (0.05 mg in 0.05 mL) every four weeks until the macular findings were considered to be dry. Fluorescein angiography and optical coherence tomography were used for the diagnosis and for the checks which were carried out every twelve weeks. The visual acuity was measured with an ETDRS chart. RESULTS: The treatment with Avastin is completed in 319 eyes with an average improvement of the visual acuity of 5.1 letters after 3.3 injections, and with Lucentis in 226 eyes with an average improvement of the visual acuity of 6.4 letters after 3.4 injections (p = 0.24; one way ANOVA). CONCLUSION: Both of the drugs allow the drying of the macular findings in the great majority of the cases after a short time and lead to a quite similar improvement of the visual acuity. A definitive stabilization of the disease after stopping the treatment is not foreseeable.

Preserved functional and structural integrity of the papillomacular area correlates with better visual acuity in retinitis pigmentosa.

PurposeLinking multifocal electroretinography (mfERG) and optical coherence tomography (OCT) findings with visual acuity in retinitis pigmentosa (RP) patients.DesignProspective, cross-sectional, nonintervention study.SubjectsPatients with typical RP and age-matched controls, who underwent SD-OCT (spectral domain OCT) and mfERG, were included.MethodsMfERG responses were averaged in three zones (zone 1 (0°-3°), zone 2 (3°-8°), and zone 3 (8°-15°)). Baseline-to-trough- (N1) and trough-to-peak amplitudes (N1P1) of the mfERG were compared with corresponding areas of the OCT. The papillomacular area (PMA) was analyzed separately. Correlations between best-corrected visual acuity (BCVA, logMAR) and each parameter were determined.Main outcome measuresComparing structural (OCT) and functional (mfERG) measures with the BCVA.ResultsIn RP patients, the N1 and N1P1 responses showed positive association with the central retinal thickness outside zone 1 (P≤0.002), while the central N1 and the N1P1 responses in zones 1, 2, and 3-with the BCVA (P≤0.007). The integrity of the IS/OS line on OCT showed also a positive association with the BCVA (P<0.001). Isolated analysis of the PMA strengthened further the structure-function association with the BCVA (P≤0.037). Interactions between the BCVA and the OCT, respectively, the mfERG parameters were more pronounced in the RP subgroup without macular edema (P≤0.020).ConclusionIn RP patients, preserved structure-function of PMA, measured by mfERG amplitude and OCT retinal thickness, correlated well with the remaining BCVA. The subgroup analyses revealed stronger links between the examined parameters, in the RP subgroup without appearance of macular edema.

A case of Erdheim-Chester disease with orbital involvement.

The Erdheim-Chester disease is a rare idiopathic, systemic, histiocytic disorder. To our knowledge, ocular involvement has been reported in only 16 cases. We describe a 55-year-old man who had symmetrical exophthalmos and several skin nodules on the arms and trunk. A magnetic resonance imaging scan confirmed the presence of bilateral, intraconal, retrobulbar tumors. An examination of the histopathologic features of orbital and skin biopsy specimens revealed xanthogranulomatous infiltrate with Touton giant cells. Further systemic investigations showed bone and retroperitoneal involvement. Three years later, multiple eyelid xanthelasmas developed in the patient. These findings are consistent with the diagnosis of the Erdheim-Chester disease. The patient's condition is stable under therapy with low-dose corticosteroids. His survival is longer than usually described in the literature.

Elevation deficit caused by accessory extraocular muscle.

PURPOSE: To report an elevation deficit, which was caused by an accessory extraocular muscle, in a 6-year-old boy. METHODS: Computed tomography and magnetic resonance imaging were used to confirm an accessory, fusiform, well-defined, solid structure in the retrobulbar space. RESULTS: A supernumerary intraconal muscle was detected between the annulus of Zinn and the posterior part of the left globe. CONCLUSION: This rare anomaly may represent an atavistic retractor bulbi muscle.