Ophthalmology

"Graefe's Archive" is a distinguished international journal that presents original clinical reports and clinically relevant experimental studies. Founded in 1854 by Albrecht von Graefe to serve as a source of useful clinical information and a stimulus for discussion, the journal has published articles by leading ophthalmologists and vision research scientists for more than a century. With peer review by an international Editorial Board and prompt English-language publication, "Graefe's Archive" provides rapid dissemination of clinical and clinically related experimental information.

Correction to: Intravitreal bevacizumab injections combined with laser photocoagulation for adult-onset Coats' disease The IRB number of the published article was A-2015-016 (page 1512, 1st paragraph of the method section).

Transcaruncular laser-assisted StopLoss Lester Jones tube surgery for lacrimal canalicular obstructions

Optical coherence tomography angiography analysis of the choriocapillary layer in treatment-naïve diabetic eyes Abstract Purpose To evaluate the capillary flow density (CFD) of choriocapillary (CC) microvasculature using optical coherence tomography angiography (OCT-A) in diabetic eyes and the association of CFD and systemic and metabolic factors. Methods Cross-sectional study. This study enrolled 282 eyes of 146 subjects, including 43 healthy control eyes, 56 diabetic eyes without diabetic retinopathy (DR), 43 eyes with mild nonproliferative DR (NPDR), 54 eyes with moderate NPDR, 38 eyes with severe NPDR, and 48 eyes with proliferative DR (PDR). CFD was measured in the CC layer. Clinical data were collected. Multiple linear regression analyses were performed to identify associated clinical variables. Results CFD in the CC layer presented a downward trend with DR progression. Comparisons of CFD in the CC layer between adjacent stages of DR revealed significant differences between severe NPDR and PDR using both 3-mm and 6-mm scan patterns (P = 0.003, P = 0.001). CFD in the CC layer in DR with diabetic macular edema (DME) was less than that in DR without DME using both 3-mm and 6-mm scan patterns (P < 0.001, P < 0.001). Coronary artery disease and atherosclerosis in other locations, estimated glomerular filtration rate, and increased HbA1c were associated with CFD in the CC layer using both 3-mm and 6-mm scan patterns (all P values < 0.05). Conclusions OCT-A revealed decreased CFD in the CC layer in the PDR stage and the presence of DME. Diabetic patients with apparently decreased CFD should be assessed carefully under general conditions.

Five-year treatment outcomes following intravitreal ranibizumab injections for neovascular age-related macular degeneration in Japanese patients Abstract Purpose To assess the real-world 5-year treatment outcomes of ranibizumab therapy in Japanese patients with neovascular age-related macular degeneration (AMD). Methods This was a retrospective, observational, and open-label effectiveness study that included 295 eyes. The participants were patients with treatment-naïve neovascular AMD who received intravitreal ranibizumab (IVR) monthly injection at least three times as the loading phase, followed by further injections as needed (pro re nata (PRN)) and follow-up assessments for 5 years. Outcomes were determined at least 5 years after the first ranibizumab injection. Results Mean logMAR best-corrected visual acuity (BCVA) at baseline was 0.52. The mean BCVA significantly improved after three loading injections; however, it declined gradually. The BCVA at 1 year was significantly better than the baseline BCVA, whereas the 3-year, 4-year, and 5-year BCVA values were significantly lower than the baseline values. The average central foveal thickness improved significantly from 366 ± 125 μm to 268 ± 134 μm (p < 0.0001). Macular atrophy was significantly more likely to occur in cases with classic choroidal neovascularization (CNV) than in cases with other AMD (p = 0.01). Conclusions IVR is well tolerated in eyes with AMD. However, a PRN regimen for AMD may have limited real-world effectiveness for long-term maintenance of improved visual acuity. Macular atrophy may occur more frequently in classic CNV. To maintain good vision, IVR treatment should be started earlier and performed continuously.

Patient characteristics of untreated chronic central serous chorioretinopathy patients with focal versus diffuse leakage Abstract Purpose To describe the characteristics and potential differences between focal and diffuse phenotypes of untreated chronic central serous chorioretinopathy (cCSC). Methods For this study, patients were divided in two groups. Focal leakage was defined as 1 "hot spot" of leakage, whereas diffuse leakage was defined as either > 1 hot spot or a larger area of widespread leakage on FA. Clinical characteristics were assessed at presentation. After Bonferroni correction, P values < 0.00125 were deemed statistically significant. Results The focal leakage group included 68 eyes (53 males), and the diffuse leakage group included 105 eyes (88 males). Mean best-corrected visual acuity (BCVA) was 77.1 ± 8.1 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters in the focal group and 76.0 ± 9.6 ETDRS letters in the diffuse group (p = 0.440). In the focal group, mean age was 46.9 ± 8.8 years, whereas this was 49.7 ± 8.3 years in the diffuse group (p = 0.033). Mean central foveal thickness was 107.1 ± 21.3 μm in the focal group and 106.2 ± 27.3 μm in the diffuse group (p = 0.818). Mean choroidal thickness was 407.5 ± 114.8 μm in the focal group and 419.1 ± 113.9 μm in the diffuse group (p = 0.578). In the focal group, subretinal fluid was present in the fellow eye in 16% of the patients, as compared to 29% in the diffuse group (p = 0.067). Conclusions In untreated cCSC patients with focal or diffuse leakage on FA, no marked differences in clinical characteristics were found. Extensive choroidal abnormalities may be present in both groups, which are presumed to lie at the basis of the development of cCSC.

Protein kinase C-mediated insulin receptor phosphorylation in diabetic rat retina Abstract Purpose Diabetic retinopathy (DR) involves a proliferation of vascular endothelial cells and loss of pericytes. There is a link among the action of protein kinase C (PKC) and insulin signaling. Thus, we investigated the differences between these cells in insulin receptor (IR) phosphorylation in DR. Methods Retinas were removed from streptozotocin-induced diabetic or healthy rats, and IR expression levels were compared by immunoblot and immunohistochemistry. In vitro assays also were performed in order to determine the expressions of phosphorylated IR in both cells cultured under 5.5 or 25 mM glucose by immunoblot. Cell viability was determined in both cells cultured under different concentrations of phorbol myristate acetate (PMA), a PKC activator. To determine the involvement of the PI3 kinase pathway of IR, PMA with or without wortmannin-induced changes in Akt was also analyzed. Results Immunoreactivity to the IR was decreased in diabetic retina. High glucose (25 mM) increased phosphorylated IR levels in endothelial cells but not in pericytes. PMA (1 nM or higher) induced death of pericytes, while endothelial cells were increased. PMA increased phosphorylated Akt in endothelial cells and decreased in pericytes. Wortmannin suppressed the PMA-induced phosphorylation of Akt in endothelial cells. Conclusions The different responses to 25 mM glucose and PMA were observed between retinal endothelial cells and pericytes. Thus, IR phosphorylation is likely important for retinal vascular cells to survive in diabetic retina.

Elevation of the vitreous body concentrations of oxidative stress-responsive apoptosis-inducing protein (ORAIP) in proliferative diabetic retinopathy Abstract Purpose Oxidative stress has been implicated in the pathogenesis of various disorders, including diabetic retinopathy (DR). Oxidative stress-responsive apoptosis-inducing protein (ORAIP; a tyrosine-sulfated secreted form of eukaryotic translation initiation factor 5A [eIF5A]) is a recently discovered pro-apoptotic ligand that is secreted from cells in response to oxidative stress and induces apoptosis in an autocrine fashion. This study aimed to determine if ORAIP plays a role in DR. Methods To investigate the role of ORAIP in DR, we analyzed the levels of ORAIP in the vitreous body and their relationship with the extent of proliferative diabetic retinopathy (PDR). Enzyme-linked immunosorbent assay was used to quantify the levels of ORAIP, vascular endothelial growth factor (VEGF), C–C motif chemokine ligand 2 (CCL2), interleukin-6 (IL-6), and IL-8 in the vitreous body of 40 eyes from 28 patients with PDR and 11 patients with non-PDR (NPDR). We also analyzed the expression of ORAIP in insoluble proliferative tissues from vitreous body samples by immunofluorescent staining. Results The vitreous body concentration of ORAIP was significantly (P = 0.0433) higher in the PDR group (52.26 ± 8.68 [mean ± SE] ng/mL, n = 29) than in the NPDR group (28.21 ± 7.30 ng/mL, n = 11). However, there were no significant correlations between the concentration of ORAIP and those of VEGF, IL-6, CCL2, or IL-8. ORAIP expression was observed in the insoluble proliferative tissues in vitreous body samples of most patients in the PDR group, whereas almost no expression of ORAIP was observed in patients in the NPDR group. Conclusions Our findings strongly suggest that ORAIP plays a role in oxidative stress-induced retinal injury and may be a sensitive diagnostic marker and a promising therapeutic target for oxidative stress-induced cytotoxicity.

Ocular alterations, molecular findings, and three novel pathological mutations in a series of NF2 patients Abstract Purpose To evaluate ophthalmological and molecular findings in eight patients with a clinical diagnosis of neurofibromatosis type 2 (NF2). New pathological mutations are described and variability in the ophthalmic phenotype and NF2 allelic heterogeneity are discussed. Methods Eye examination was performed in eight NF2 patients, and it included the measurement of the visual acuity, biomicroscopy, dilated fundus examination, color fundus photography, infrared photography, and spectral domain optical coherence tomography (SD-OCT). Molecular analysis was performed with whole-exome sequencing using DNA derived from peripheral blood mononuclear cells from each individual. Results Ophthalmological features were present in all patients, ranging from subtle retinal alterations identified only using SD-OCT to severe ocular damage present at birth. Six mutations were observed: two patients with stop codon mutation as shown on table 1 and result section, three patients with frameshift mutation as shown on table 1 and result section. Three novel mutations were found among them. Conclusions It is a descriptive study of a rare disease, with poor previous literature. Clinical and genetic data are shown, reviving the need to further studies to clarify the genotype-phenotype correlations in NF2.

Usefulness of the dacryoscintigraphy in patients with nasolacrimal duct obstruction prior to endoscopic dacryocystorhinostomy Abstract Purpose To evaluate the clinical usefulness of the dacryoscintigraphy in patients with nasolacrimal duct obstruction prior to endoscopic dacryocystorhinostomy. Methods One hundred thirty-five lacrimal views of endoscopic dacryocystorhinostomy (DCR) with a single surgeon for primary nasolacrimal duct obstruction (PANDO) were included. These were assigned into three groups according to the type of dacryoscintigraphy. Group 1 was a pre-sac obstruction pattern. Group 2 was an intra-sac obstruction pattern. Group 3 was post-sac obstruction pattern. Each group was evaluated for an anatomical and functional surgical success, presence of complications including granuloma, synechiae, and tube-induced inflammation at least 12 months after the surgery. Results Both anatomical and functional success rate showed no significant difference among the three groups (P = .297 and .472 linear by linear association). Functional failure rate (functional failure/total failure) also showed no clinically significant differences between groups. Logistic regression analysis was performed to determine the factors associated with functional success. There were no statistically significant factors in age, sex, scintigraphy type, pre-operative endoscopic grade, post-operative granuloma, and synechiae. Conclusion In patients with nasolacrimal duct obstruction, preoperative evaluation of obstruction level using dacryoscintigraphy may be not useful for predicting the functional success of the endoscopic dacryocystorhinostomy.

Use of low-vault posterior chamber collagen copolymer phakic intraocular lenses for the correction of myopia: a 3-year follow-up Abstract Background Phakic intraocular lens (pIOL) models have indicated an association between cataract formation and inadequate vaulting. In this study, the efficacy and safety of low-vault posterior chamber pIOLs in the correction of myopia were examined over 3 years. Methods From 316 patients undergoing surgery, 14 eyes with a low vault (≤ 150 μm) were examined from 14 patients. After implanting the Visian Implantable Collamer pIOL for the correction of myopia (moderate and high), the pIOL vault, endothelial cell loss, uncorrected distance visual acuity (UDVA), corrected DVA (CDVA), and detrimental events were examined over 3 years. Results Based on the findings, the mean spherical equivalent reduced from − 8.15 ± 3.29 before surgery to − 1.02 ± 0.75 diopters 3 years after the surgery. In terms of visual outcomes, the mean UDVA (Log MAR) significantly increased from 0.95 ± 037 to 0.27 ± 0.28, and the mean CDVA also increased from 0.99 ± 0.11 to 0.06 ± 0.08 (P < 0.05). The mean indices of safety and efficacy were respectively 1.075 and 0.748. The eyes lost not more than two visual acuity lines. Based on the findings, 82% achieved 0.80 or better CDVA, while the total endothelial cell loss was 7.96% during 3 years. Overall, vision-threatening conditions were not reported. Conclusion The introduced pIOL can be considered a safe and efficient method for myopia at moderate to high levels.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com