Murat Kucukevcilioglu

Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus

Significance Diabetic retinopathy (DR), a primary cause of blindness, is characterized by microvascular abnormalities. Recent evidence suggests that retinal diabetic neuropathy (RDN) also occurs in people with diabetes, but little is known about the temporal relationship between DR and RDN. This longitudinal study in people with diabetes with no or minimal DR shows that RDN precedes signs of microvasculopathy and that RDN is progressive and independent of glycated hemoglobin, age, and sex. This finding was further confirmed in human donor eyes and in two experimental mouse models of diabetes. The results suggest that RDN is not ischemic in origin and represent a shift in our understanding of the pathophysiology of this complication of diabetes that potentially affects vision in all people with diabetes mellitus. Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 μm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 μm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 μm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 μm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced “type 1” and B6.BKS(D)-Leprdb/J “type 2” diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.

Comparison of Retinal and Choriocapillaris Thicknesses Following Sitting to Supine Transition in Healthy Individuals and Patients With Age-Related Macular Degeneration

IMPORTANCE The effects of position on retinal and choroidal structure are absent from the literature yet may provide insights into disease states such as age-related macular degeneration (AMD). OBJECTIVE To evaluate the effect of postural change on retinal and choroidal structures in healthy volunteers and patients with non-neovascular AMD. DESIGN, SETTING, AND PARTICIPANTS Prospective observational case series at an academic tertiary care retina service from September 2013 to April 2014 involving 4 unaffected volunteers (8 eyes) and 7 patients (8 eyes) with intermediate AMD. Healthy volunteers selected for the study had no evidence of ocular disease. Patients with AMD were required to have at least 10 intermediate-sized drusen. EXPOSURES Spectral-domain optical coherence tomography with enhanced depth imaging in upright (sitting) and supine positions. Stable imaging was achieved using a rotating adjustable mechanical arm that we constructed to allow the optical coherence tomography transducer to rotate 90°. The Iowa Reference Algorithms were used to quantify choroid and choriocapillaris thicknesses. MAIN OUTCOMES AND MEASURES Changes in sitting and supine position central macular thickness (in micrometers), total macular volume (in cubic millimeters), choroidal thickness (in micrometers), and choriocapillaris-equivalent thickness (CCET, in micrometers). RESULTS Choriocapillaris-equivalent thickness was thinner in healthy participants (9.89 μm; range, 7.15-12.5 μm) compared with patients with intermediate AMD (16.73 μm; range, 10.31-27.38 μm) (P = .02); there was no difference in overall choroidal thickness between the 2 groups (P = .38). There was a 15% CCET reduction among healthy participants when transitioning from a sitting (9.89 μm) to supine (8.4 μm; range, 6.92-10.7 μm) position (P = .02) vs a CCET reduction of 11.1% from sitting (16.73 μm) to supine (14.88 μm; range, 8.76-20.8 μm) positioning (P = .10) in patients with intermediate AMD. CONCLUSIONS AND RELEVANCE Intermediate AMD appears to be associated with an increase in CCET and with a lack of positional responses that are observed in the CCET of normal eyes. Our results suggest that although outer portions of the choroid do not appear to be responsive to modest positional or hydrostatic pressure, the choriocapillaris capacity is, and this is measurable in vivo. Whether this physiologic deviation that occurs in AMD is related to atrophy, inflammation, or changes in autoregulatory factors or growth factors remains to be determined.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Novel Biomarkers of Primary Open-Angle Glaucoma.

Purpose:We aimed to assess the levels of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with primary open-angle glaucoma (POAG) and to compare the NLR and PLR results of patients with POAG and ocular hypertension, as well as in healthy controls. Patients and Methods:Eighty-four patients with POAG, 94 patients with ocular hypertension, and 80 healthy subjects were enrolled in this retrospective study. Complete ophthalmological examination and complete blood count measurements were performed for all subjects. Results:There was a significant difference in the NLR (P=0.003) and PLR (P=0.049) between POAG and control groups. In addition, there was a correlation between pattern standard deviation and NLR in the POAG group. The receiver operating characteristics analysis revealed that the value of NLR to distinguish patients with POAG and controls was found to be 0.651. The best cutoff value was 2.1, with a sensitivity of 65% and a specificity of 65%. Conclusions:Our study for the first time provides evidence that NLR and PLR may be useful as biomarkers in patients with POAG.

Pars plana vitrectomy versus three intravitreal injections of bevacizumab for nontractional diabetic macular edema: A prospective, randomized comparative study.

Background: The aim of this study was to compare the effectiveness of pars plana vitrectomy (PPV) and removal of the internal limiting membrane (ILM) with three, monthly, intravitreal bevacizumab (IVB) injections for refractory diabetic macular edema. Materials and Methods: This was a prospective, randomized, comparative, interventional study. Forty-four patients were enrolled and randomized in two groups. Twenty-two eyes enrolled in Group I received three IVB injections at monthly interval. Twenty-two eyes were enrolled in Group II which underwent PPV with ILM removal. The primary outcomes measured were: (1) Best corrected logMAR visual acuity (BCVA) using Snellens visual acuity chart. (2) Central macular thickness (CMT) on optical coherence tomography. The secondary outcome measures were: Complication rates like (1) progression of lens opacities, (2) high intraocular pressure needing further treatment/procedure, (3) development of vitreous hemorrhage related to the procedure employed, (4) retinal detachment and (5) severe inflammation/endophthalmitis. Results: In Group I (IVB): 3 (13.6%) eyes showed no change in BCVA; 3 (13.6%) eyes reported decrease in BCVA and 16 (72.8%) eyes showed improvement in BCVA; (P = 0.0181). In Group II (PPV): 4 (18.2%) eyes showed no change in BCVA; 5 (22.7%) eyes showed decrease and 13 (59.1%) eyes showed improvement in BCVA (P = 0.0281). Mean decrease in CMT in IVB group was 108.45 μ, whereas mean decrease in CMT in PPV group was 161.36 μ. No major complications were seen in either group. Conclusion: Posttreatment decrease in CMT was more in PPV group and vision improvement more in IVB group. However, no statistically significant difference between the two methods was found.Background: The aim of this study was to compare the effectiveness of pars plana vitrectomy (PPV) and removal of the internal limiting membrane (ILM) with three, monthly, intravitreal bevacizumab (IVB) injections for refractory diabetic macular edema. Materials and Methods: This was a prospective, randomized, comparative, interventional study. Forty-four patients were enrolled and randomized in two groups. Twenty-two eyes enrolled in Group I received three IVB injections at monthly interval. Twenty-two eyes were enrolled in Group II which underwent PPV with ILM removal. The primary outcomes measured were: (1) Best corrected logMAR visual acuity (BCVA) using Snellens visual acuity chart. (2) Central macular thickness (CMT) on optical coherence tomography. The secondary outcome measures were: Complication rates like (1) progression of lens opacities, (2) high intraocular pressure needing further treatment/procedure, (3) development of vitreous hemorrhage related to the procedure employed, (4) retinal detachment and (5) severe inflammation/endophthalmitis. Results: In Group I (IVB): 3 (13.6%) eyes showed no change in BCVA; 3 (13.6%) eyes reported decrease in BCVA and 16 (72.8%) eyes showed improvement in BCVA; (P = 0.0181). In Group II (PPV): 4 (18.2%) eyes showed no change in BCVA; 5 (22.7%) eyes showed decrease and 13 (59.1%) eyes showed improvement in BCVA (P = 0.0281). Mean decrease in CMT in IVB group was 108.45 μ, whereas mean decrease in CMT in PPV group was 161.36 μ. No major complications were seen in either group. Conclusion: Posttreatment decrease in CMT was more in PPV group and vision improvement more in IVB group. However, no statistically significant difference between the two methods was found.

Bilateral Symmetrical Subepidermal Calcified Nodules of the Eyelids

Abstract A subepidermal calcified nodule is an uncommon variant of calcinosis cutis and only a limited number of cases have been reported about the eyelid nodules in the literature. A 20-year-old male was referred to our department with symmetrical nodules on both upper eyelids enlarging over 3 years. Both nodules were removed by excisional biopsy. After the histopathologic evaluation, the diagnosis was subepidermal calcified nodule. He had a complete recovery with no recurrence and acceptable aesthetic appearance. As a rare entity, subepidermal calcified nodule should be thought in differential diagnosis of eyelid nodular lesions and symmetrical appearance may be seen.

Outcomes of Intravitreal Dexamethasone Implant in the Treatment of Recalcitrant Diabetic Macular Edema

Objectives: To investigate the efficacy and safety of intravitreal dexamethasone (OZURDEX®) implantation in patients with recalcitrant diabetic macular edema. Materials and Methods: This is a retrospective non-randomized study of patients who underwent intravitreal dexamethasone implantation for recalcitrant diabetic macular edema. Main outcome measures included changes in best corrected visual acuity (BCVA), central macular thickness (CMT), and incidence of ocular side effects. Results: Fifty-seven eyes of thirty-eight patients (20 females, 18 males; mean age 65±7 years) were included in the study. The mean hemoglobin A1c level was 7.9±1.7%. Before entering the study, patients had undergone 5.71±3.40 anti-vascular endothelial growth factor (anti-VEGF) and 3.44±2.46 intravitreal triamcinolone acetonide injections. The mean duration of diabetes and diabetic macular edema was 17.2±6.4 years and 60.2±17.6 months, respectively. At baseline, mean CMT was 506.76±166.74 µm, and the mean BCVA was 0.68±0.38 LogMAR. Mean CMT significantly decreased to 341.36±146.26 µm (p<0.001), 324.41±114.58 µm (p<0.001), and 384.82±151 µm (p<0.001) at 1, 3, and 4 months of follow-up and increased again to 462.29±152.87 µm at 5 months. Sixteen eyes (28%) received second injections after mean of 7.4±2.3 months and mean CMT was again significantly decreased at 7, 8, and 9 months. Significant improvement in mean BCVA (0.54±0.41 LogMAR; p<0.001) occurred only at 1 month after implantation. However, subgroup analysis revealed significant BCVA improvement in the pseudophakic group at 1, 3, and 4 months. Among phakic patients, 50% showed cataract progression and 28% had elevated intraocular pressure increase which was managed medically. Conclusion: Intravitreal dexamethasone implantation was effective for the first 4 months in eyes with recalcitrant diabetic macular edema. However, it is hard to displace anti-VEGF agents as first-line therapy due to steroid-related complications.

Localized flap melt after Nd-YAG laser treatment in recurrent post-LASIK epithelial ingrowth

Neodymium: Yttrium-Aluminum-Garnet (Nd-YAG) laser treatment of epithelial ingrowth was found promising with high success rates in cases of primary post-LASIK epithelial ingrowth. However, the application range of this procedure is not well-known. For the first time, the authors report the outcome of a patient treated with Nd-YAG laser for multiple recurrences of post-laser in situ keratomileusis epithelial ingrowth.

Is there a relationship between outer retinal destruction and choroidal changes in cone dystrophy

Purpose: The aim of the present study was to use enhanced depth imaging optical coherence tomography (EDI-OCT) to investigate choroidal changes in patients with cone dystrophy (CD) and to correlate these findings with clinical and electroretinography (ERG) findings. Methods: This case-control study included 40 eyes of 20 patients with CD and 40 eyes of 40 age- and refraction-matched healthy individuals. Choroidal thickness (CT) measurements were obtained under the foveal center and at 500 and 1,500 μm from the nasal and temporal regions to the center of the fovea, respectively. EDI-OCT and ERG data were analyzed, and the correlations of CT with the best-corrected visual acuity (BCVA) and the central foveal thickness (CFT) were evaluated. Results: The mean subfoveal CTs in the CD and control groups were 240.70 ± 70.78 and 356.18 ± 48.55 μm, respectively. The subfoveal CT was significantly thinner in patients with CD than in the controls (p<0.001). The patients with CD also had significantly thinner choroids than the controls at each measurement location relative to the fovea (p<0.001). The subfoveal CT in the CD group correlated with CFT (p=0.012), but no significant correlation was found between the subfoveal CT and BCVA or photopic ERG responses. Conclusions: The present study demonstrated a significant thinning of the choroid in patients with CD. EDI-OCT is a useful technique for describing the choroidal changes occurring in CD. Future studies investigating the association between choroidal changes and outer retinal destruction or the disease stage may provide a better understanding of the pathophysiology of CD.

Surgical Outcomes of Idiopathic Epiretinal Membrane: the Gülhane Experience

Objectives: We aimed to report our experiences and outcomes of vitreoretinal surgery in idiopathic epiretinal membrane. Materials and Methods: We retrospectively reviewed patients who underwent vitreoretinal surgery for idiopathic epiretinal membrane between January 2012 and 2014. The patients’ pre- and postoperative visual acuity, slit-lamp examination findings, and optical coherence tomography (OCT) images were evaluated. Results: Forty-five eyes of 45 patients (36% male, 64% female) were included (mean age, 69±8.2 years). Mean postoperative follow-up time was 7±4 (1-12) months. The mean preoperative logMAR best corrected visual acuity was 0.58±0.32 and postoperatively 0.40±0.31, 0.33±0.33, 0.28±0.34 respectively at 3, 6, and 12 months. All OCT parameters showed statistically significant anatomical improvement at 1, 3, 6, and 12 months. Correlation analysis showed that central macular thickness (r=0.69, p<0.05) and central macular volume (r=0.69, p<0.05) were the only parameters that had strong positive correlations with visual improvement. Conclusion: Epiretinal membrane causes heterogeneous anatomical changes in the macula for every patient. Therefore, a correlation between visual gain and changes in central macular thickness could not yet be demonstrated. We believe that central macular volume may be a better parameter for following these patients.

Clinical features and management of dacryops

ABSTRACT Purpose: To describe clinical, imaging findings, and management of dacryops cases. Methods: A retrospective chart review was performed to identify the patients diagnosed with dacryops over a 5-year period. The clinical features based on clinical findings, computerized tomography and ultrasonography, and observation and surgical excision results were noted when available. Results: We included 14 eyes of 14 patients. Seven (50%) were men with a median age of 48 years. The most common symptom was non-painful upper eyelid mass. All patients had the visible protruding cyst while eversion of the upper eyelid. Imaging studies, including orbital computerized tomography and ultrasonography were performed in six cases. Histological assessment of the excised cyst was done in two cases. Surgical excision was performed in five (36%) cases and observation was elected for nine (64%) cases. The median follow-up was 30 months. There was no recurrence of cysts in patients underwent surgery and the symptoms were not deteriorated in patients elected observation. Conclusion: Dacryops is a rare clinical entity that can be diagnosed easily with or without imaging methods. Surgical excision of the cyst could be curative and observation is also a safe method in selected cases.