Examining the correlation of lymphangiogenesis biomarkers with clinical condition in Age-Related Macular Degeneration (AMD).

The aim of this study is to investigate the relationship between age-related macular degeneration (AMD) and lymphangiogenesis biomarkers, namely LYVE-1, Podoplanin, VEGF-C, VEGFR-2 and VEGFR-3. This prospective and interventional study includes 30 patients with AMD which may be dry or wet type and 30 controls for whom vitrectomy and phacoemulsification was indicated due to additional pathologies (epiretinal membrane, macular hole, retinal detachment, and cataract). 0.1-0,2 ml of aqueous humor and 0.5-1 ml of vitreous sample was taken during the operations. Before the operations 1 tube serum was also taken. All the lymphangiogenesis biomarkers in the study are examined by ELISA method. LYVE-1 (p = 0.001) and Podoplanin (p = 0.004) levels in the vitreous for the patient group are found to be significantly lower than the control group. Serum (p = 0.019), vitreous (p = 0.001), aqueous (p < 0.001) levels of VEGF-C for the patient group are significantly higher than the control group. VEGF-C/VEGFR-2 (p < 0.001), VEGF-C/VEGFR-3 (p < 0.001) ratios in the vitreous for the patient group are found to be significantly higher than the control group. Especially in wet AMD patients, LYVE-1 level is significantly lower in the vitreous (p = 0.002) and aqueous (p = 0.002) than the control group. In addition, Podoplanin level is observed as significantly lower in the vitreous (p = 0.014) and serum (p = 0.002) in comparison to control group. In the wet AMD group, VEGF-C level in the vitreous (p < 0.001), aqueous (p < 0.001) and serum (p = 0.001) is higher than the control group. The result of this study indicates a valid relationship between the weakening of lymphangiogenesis and the pathophysiology of AMD, especially for the wet type. It is observed that the levels of receptors that bind VEGF-C (VEGFR-2 and VEGFR-3) do not increase at the same rate as VEGF-C to compensate for the increase in VEGF-C. The absence of an increase in VEGFR-3, which is especially necessary for lymphangiogenesis, also suggests that lymphangiogenesis is weakened or decreased in AMD. In the future interventional studies with larger series, examination of lymphangiogenic biomarkers in inflammatory retinal diseases and glaucoma may reveal unexplored details.

Real Life Multicenter Comparison of 24-Month Outcomes of Anti-VEGF Therapy in Diabetic Macular Edema in Turkey: Ranibizumab vs. Aflibercept vs. Ranibizumab-Aflibercept Switch.

The aim of this study was to compare the outcomes of diabetic macular edema (DME) treated with aflibercept (AFB) or ranibizumab (RNB) only, and after switching from RNB to AFB. This was a retrospective, real-world, multicenter (7 cities) 24 month study. Overall, 212 eyes in the AFB group, 461 in the RNB group, and 141 in the RNB to AFB group were included. The primary endpoints were differences in visual acuity (VA) and central macular thickness (CMT) from baseline to the final visit. The secondary outcomes were the percentage of eyes that achieved ≥10 letters gain and ≥10 letters loss in vision at month 12 and 24, and the percentage of eyes that achieved a thinning of ≥20% in CMT at month 3 and month 6. The results showed that VA did not significantly differ at baseline (AFB: 0.62 ± 0.38, RNB: 0.61 ± 0.36, RNB to AFB: 0.61 ± 0.38), at checkpoints, or at the final visit (AFB: 0.46 ± 0.38, RNB: 0.5 ± 0.37, RNB to AFB: 0.53 ± 0.36) (p > 0.05). Though the mean CMT at baseline was significantly thicker in the RNB to AFB group (479 ± 129.6 µm) when compared to the AFB (450.5 ± 122.6 µm) and RNB (442 ± 116 µm) groups (p < 0.01), similar measurements were obtained after 12 months. The percentages of eyes that gained or lost ≥10 letters in the AFB, RNB, and RNB to AFB groups at year 1 and 2 were similar, as was the percentages of eyes that demonstrated ≥20% CMT thinning at month 3 and 6. Our study showed similar visual improvements in non-switchers (AFB and RNB groups) and switchers (RNB to AFB group) through 2 years follow-up, however, AFB patients required fewer injections, visits, or need for additional treatments.

The effect of longstanding silicone oil on retina choroid and optic nerve in eyes with retinal detachment: an optical coherence tomography study.

BACKGROUND: The study aims to evaluate peripapillary retinal nerve fiber layer thickness (RNFL-T), central macular thickness (MT), choroidal thickness (CT), and thickness of each retinal layer after automatic segmentation in patients who underwent retinal detachment (RD) repair with longstanding silicone oil tamponade. METHODS: We enrolled 33 patients who underwent complicated primary rhegmatogenous RD surgery and followed up with a long-term silicone tamponade were included in this retrospective comparative (case-control) study. RNFL-T, CT, and thickness of each retinal layer after automatic segmentation analysis were measured after the longstanding silicone removal surgery. RESULTS: The mean silicone oil removal time was 15.1 ± 15.2 (7-70) months. The overall average thickness of the RNFL was 90.7 ± 13.6 µm in the operated eyes and 118.3 ± 35.6 µm in the sound eyes, with a statistically significant difference. The overall average central MT was 186.3 ± 57.7 µm and was significantly lower in the operated eyes than in the sound eyes. Inner retinal layers of the study group showed a significant thinning in the nerve fiber layer, ganglion cell layer, inner plexiform layer, and inner nuclear layer as compared to that of the sound eyes. The subfoveal CT was 213.7 ± 86.6 µm in the study eyes and 217.7 ± 115.5 µm in the control eyes. There was no significant difference between the study eyes and controls. CONCLUSION: The effects of silicone oil on the retina remain uncertain; however, morphological results in our study have shown direct or indirect silicone oil-induced toxicity, especially in the inner retinal layers.

Anti-vascular endothelial growth factor therapy in diabetic macular edema: real-life outcomes from a multicenter study in Turkey over 36 months.

PURPOSE: This study aimed to report the visual and anatomical outcomes of intravitreal anti-VEGF treatment for diabetic macular edema (DME) in a real-world clinical setting from Turkey over 36 months. METHODS: This is a retrospective, multicenter (7 sites) study. The medical records of 1072 eyes (both previously treated and naive eyes) of 706 consecutive patients with visual impairment due to center-involving DME treated with intravitreal anti-VEGF injections between April 2007 and February 2017 were reviewed. The eyes were divided into mutually exclusive three groups based on the duration of follow-up (12, 24, or 36 months). Primary outcome measures were changes in visual acuity (VA) and central macular thickness (CMT) from baseline to final visit in each cohort, frequency of visits and intravitreal anti-VEGF injections. As secondary endpoints, VA outcomes were assessed in subgroups stratified by baseline VA [<70 ETDRS letters and ≥70 ETDRS letters] and loading dose status of anti-VEGF injections. RESULTS: VA increased by a mean of 8.2 letters (12-month cohort, p < 0.001), 5.3 letters (24-month cohort, p < 0.001), and 4.4 letters (36-month cohort, p = 0.017) at final visits. The eyes with <70 VA letters achieved more significant VA improvement at final visits in all cohorts compared with eyes with >70 VA letters (p < 0.001). The mean decreases in CMT from baseline to last visits at 12-, 24-, and 36- month cohorts were -100.5 µm, -107.7 µm, and -114.3 µm, respectively (p < 0.001). The mean number of injections given were 4.6, 2.3, and 1.8 during years 1 to 3, respectively. Patients who received loading dose showed greater VA gains than those who did not in all follow-up cohorts. CONCLUSION: Our study revealed that anti-VEGF treatment improved VA and CMT over a follow-up of 36 months. Although these real-life VA outcomes following anti-VEGF therapy for DME were similar to other real-life studies, they were inferior to those noted in randomized controlled trials, mainly due to undertreatment.

Evaluation of static and dynamic Pupillometry changes in men using Silodosin for benign prostatic hypertrophy.

BACKGROUND: Intraoperative floppy iris syndrome is a variant of the small pupil syndrome that has been observed during cataract surgery in some patients currently or previously treated with α1 adrenergic blockers. It is important for cataract surgeons to predict the probable complications preoperatively. Our study aims to evaluate the static and dynamic pupil characteristics of patients treated with silodosin-a selective α1 adrenergic blocker-for benign prostate hypertrophy (BPH) and to compare these values with healthy subjects using an automatic quantitative pupillometry system. METHODS: A total of 74 BPH patients treated with silodosin for six months (group 1) and 30 healthy subjects (group 2) were enrolled in this prospective multidisciplinary cross-sectional study. Static and dynamic pupillometric measurements were obtained under optimized conditions, and the results were compared between the two groups. RESULTS: Seventy-four male patients with a mean age of 63,35 ± 7,21 (46-77) years with BPH treated with silodosin and 30 normal male subjects with a mean age of 63,07 ± 4,73 (52-71) years were analyzed. There were statistically significant differences between the groups with regard to scotopic pupil diameter (PD), high photopic PD, and low photopic PD (p < 0.001, for each one). The patient group had statistically significant higher values of amplitude and velocity of pupil contraction and lower values of duration of pupil contraction and latency as well as duration and velocity of pupil dilation. CONCLUSION: The static and dynamic pupil characteristics of subjects treated with silodosin for BPH are different from those of healthy eyes. In addition, our results may have shed light on the risk for intraoperative floppy iris syndrome (IFIS) before cataract surgery; thus, surgeons can be alert and take precautions.

Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in 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)-Lepr(db)/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.

Macular sensitivities measured by microperimetry in patients on hydroxychloroquine treatment.

PURPOSE: To examine retinal sensitivity in patients on hydroxychloroquine (HCQ) with no evidence of retinopathy. MATERIALS AND METHODS: Seventy patients on HCQ and 30 healthy control subjects were included prospectively. All subjects underwent complete ophthalmic examination including best corrected visual acuity, tonometry, colour vision testing, biomicroscopy of anterior segment, dilated fundoscopy, 10-2 visual field testing, and spectral domain optical coherence tomography. The patients and control subjects who met the inclusion criteria and had normal tests underwent microperimetry (MP) testing. First, all patients were compared with the control group. Secondly, patients were divided into three sets of groups based on (1) duration of use ≤5 years (DOU≤5) and >5 years (DOU>5), (2) daily dose ≤5 mg/kg/day (DD≤ 5) and >5 mg/kg/day (DD>5), and (3) a cumulative dose ≤1000 gr (CD≤ 1000) and >1000 gr (CD>1000), and these groups were compared to each other and to the control group. A correlation analysis was also performed between MP sensitivity and DOU, DD, and CD. RESULTS: Seven patients on HCQ showing visual field abnormality were excluded which yielded 63 patients and 30 control subjects for the final analysis. We observed significant differences only in the central region but not in the paracentral or peripheral regions on MP in HCQ users. The median MP sensitivities in the central region were significantly lower in all the patients [84 (63-100) dB], and in subgroups of DOU >5 [84 (63-99) dB], DD >5 [82 (63-97) dB] and CD >1000 [82 (63-92) dB] when compared to controls [89.7 (83-98) dB]. A statistically significant correlation was found only between DD and MP sensitivity in the central region (r = -0.263; p = 0.02). CONCLUSIONS: MP sensitivities in the central macula were significantly lower in patients taking HCQ for more than 5 years, at a daily dose more than 5 mg per day, and with a cumulative dose over 1000 gr. Further research investigating long-term follow-up changes in MP sensitivities is needed to determine cutoff values for early retinal toxicity.

Clinical features and management of dacryops.

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.

The effects of amphotericin B on angiogenesis in chick chorioallantoic membrane.

OBJECTIVE: Amphotericin B (AmB) is widely used as a mainstay in the treatment of sight-threatening fungal endophthalmitis. From the time that itraconazole was discovered to have a previously unknown anti-angiogenic activity, we have suspected that AmB may have possible effects on ocular angiogenesis. The purpose of this study was to evaluate the in vivo anti-angiogenic effect of AmB in the chick chorioallantoic membrane (CAM) model. MATERIALS AND METHODS: Atak-S type fertilized eggs obtained from the Poultry Institution were used. The eggs were kept under 37 °C at 85-90% relative humidity throughout the experiment. Amphotericin B was prepared in two different concentrations (AmB 125 µg/1 mL and 0.125 µg/1 mL). The CAMs treated with sterile distilled water was specified as controls. About 0.1 mL of each containing 12.5 and 0.0125 µg of AmB, respectively, were dropped to CAM surface. Thirteen eggs were used for each group. The results were evaluated at the 48th hour of the administration of the drugs and recorded by digital camera. RESULTS: A reduction of angiogenesis in CAM area which treated with 125 µg/1 mL of AmB was appreciable macroscopically. The affected areas showed impaired radial arrangement of small vessels with the presence of avascular zone at periphery. The dose of 0.125 µg/1 mL AmB did not show any visible anti-angiogenic effect. Numerous blood vessels with a radially arranged pattern developed toward the periphery after 48 h of treatment. In the CAMs that treated with distilled water, physiological angiogenesis was observed in allantoic vessels. Vessel formation seems to be similar in CAMs treated with 0.125 µg/1 mL AmB with the presence of visibly non-malformed alive embryos. CONCLUSIONS: The present study gives the impression that AmB has the capacity to serve as an anti-angiogenic treatment. As it is a preliminary CAM study only, further studies on both animals and humans are required.

Clinically detectable drusen domains in fibulin-5-associated age-related macular degeneration (AMD) : Drusen subdomains in fibulin-5 AMD.

To evaluate whether drusen of subjects with fibulin-5 mutation-associated age-related macular degeneration (AMD) have clinically demonstrable drusen domains as evidenced by differences between color and fluorescein angiographic profiles. Of seven patients we identified with AMD due to mutations in the fibulin-5 gene (Fib-5 AMD), five had color fundus photography and fluorescein angiography (FA). One had bilateral choroidal neovascularization and no drusen. For each eye, the green channel (GC) of the digital RGB (Red-Green-Blue) color image and hyperfluorescent domain (HD) intensity of the FA image were registered and drusen were manually segmented and measured. Totally 75 small (≤62 µm), 110 intermediate (63-125 µm), and 30 large (>125 µm) drusen were measured in four patients within the 6 × 6 mm central macular areas. All four subjects demonstrated central or paracentral HDs within each drusen perimeter. HDs were found in association with each druse, with a HD/GC ratio of 0.82, 0.76, and 0.72 respectively for small, intermediate, and large drusen (Student T Test: P < 0.01, P < 0.01, P < 0.01). A statistical difference was found for the HD/GC ratios between small- and intermediate-sized drusen and small- and large-sized drusen but not between intermediate-sized and large-sized drusen (P = 0.001, P < 0.001, P > 0.05, respectively). AMD patients with mutations in fibulin-5 share drusen phenotypic structure and have HD/GC ratios that are similar to individuals with cuticular or basal laminar drusen. Drusen substructure may reflect similarities in drusen stage and/or genesis and appear to vary among AMD genotypes.

Prostaglandin associated periorbitopathy in patients using bimatoprost, latanoprost and travoprost.

BACKGROUND: To investigate the frequency of prostaglandin-associated periorbitopathy among bimatoprost, latanoprost and travoprost users. DESIGN: Retrospective observational case series. PARTICIPANTS: The study group included 105 patients who were using one of the drugs in one eye for more than 1 month, and the other eye was used as a control. MAIN OUTCOME MEASURES: The frequency of prostaglandin-associated periorbitopathy. METHODS: Special care was taken to detect five prostaglandin-associated periorbitopathy findings. Hertel exophthalmometry measurements and colour pictures of the periocular area were taken. RESULTS: Statistically significant differences were found among the groups regarding the presence of all prostaglandin-associated periorbitopathy findings (P < 0.05). Periorbital fat loss was the most frequent and was observed in nearly all prostaglandin-associated periorbitopathy patients except those who were relatively young. The overall frequency of prostaglandin-associated periorbito pathy was 93.3% in the bimatoprost group, 41.4% in the latanoprost group and 70% in the travoprost group. The frequency of deepening of the upper lid sulcus was 80% in the bimatoprost group, 15.7% in the latanoprost group and 45% in the travoprost group. The frequency of milder changes (the presence of either only periorbital fat loss or dermatochalasis involution or the presence of both) was higher in the latanoprost group (62%) than in the travoprost (35.7%) and bimatoprost (7.1%) groups. CONCLUSIONS: Prostaglandin-associated periorbitopathy is as common as other adverse effects when careful examinations are performed and is more frequent and more severe in bimatoprost users. The loss of the periorbital fat pad is the first sign to occur during the evolution of prostaglandin-associated periorbitopathy, especially in older patients.

Bilateral symmetrical subepidermal calcified nodules of the eyelids.

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.

Risk factor analysis for long-term unfavorable ocular outcomes in children treated for retinopathy of prematurity.

The aim in this study was to report long-term ocular outcomes of neonates treated for retinopathy of prematurity (ROP) and potential risk factors for unfavorable ocular outcomes. The study consisted of neonates treated for ROP between March 1999 and November 2009. Data relating baseline characteristics and late structural, functional and refractive ocular outcomes were recorded. The association between the unfavorable ocular outcomes and ROP-related risk factors was evaluated by regression analysis. Forty-eight children were included for assessment. Average chronological age at the time of followup was 3.11±0.73 years. The rates of unfavorable structural and functional outcomes were 12% and 15.3%, respectively. Ocular deviation was common (27.1%), and mostly esotropic (12/13). A clear myopic tendency was observed (51.2%), and the mean spherical equivalent per eye was -0.72±2.9 diopters. Regression analyses for unfavorable ocular outcomes revealed intraventricular hemorrhage as a core independent risk factor. In conclusion, ROP treatment has shown promising results in both structure and function. Because of the high risk of developing an unfavorable outcome, a more intense follow-up is required in neonates with a history of intraventricular hemorrhage in the neonatal period. Further studies from other centers are needed to develop a national database, which may validate this observation.

Combat-related ocular trauma and visual outcomes during counter-terrorism urban warfare operations in Turkey.

BACKGROUND: The study was to report the clinical features and post-operative outcomes in military personnel admitted to the Ocular Trauma Center of Gülhane Training and Research Hospital after sustaining combat injuries in urban warfare. METHODS: This is a retrospective, non-comparative, interventional case series analyzing Turkish military personnel transferred to our tertiary ocular trauma center from the warfare zone and combat support hospitals. Ocular injuries were subdivided into zones and ocular trauma classification. RESULTS: There were 103 combat ocular injuries in 74 military personnel. The average age was 27.31±4.64 years (range; 21-48 years), and all were men (100%). The average follow-up was 529.34±213.98 days (288-1464 days). There were 84 open-globe and 19 closed-globe injuries. Thirty-six (34.9%) had final vision of 20/40 or better. Pars plana vitrectomy was the most common surgery (79.6%). Five eyes underwent evisceration, and seven eyes developed phthisis bulbi. The globe survival rate was 88.3%. Zone III injuries (32.2%) were the most common cause of unfavorable visual outcomes, and most injuries were caused by improvised explosive devices (IEDs) (59.2%). These devices also had the worst impact on globe survival and visual improvement. These eyes had a higher likelihood ratio of requiring globe removal surgery or developing phthisis bulbi [odds ratio: 21.5 (95% CI: 1.23-373)]. Two eyes that underwent keratoprosthesis-assisted pars plana vitrectomy followed by penetrating keratoplasty (PKP) during the same session developed PKP failure while failure was not seen in any of the cases that underwent PKP in a later session. CONCLUSION: Ocular injuries related to IEDs had the most significant impact on both visual and anatomic prognoses, and globe survival was less likely in eyes with zone III trauma, in which intraocular foreign bodies penetrated the choroid. There is a higher pos-sibility of PKP failure if this procedure is performed during the same session as other ocular surgery.

Uveitis as a Confounding Factor in Retinal Nerve Fiber Layer Analysis Using Optical Coherence Tomography.

PURPOSE: To investigate the retinal nerve fiber layer thickness (RNFLT) in uveitic eyes and search for the associations with uveitis activity, etiology and location. METHODS: The files of 76 patients with uveitis and 76 controls were scanned. Associations of RNFLT were analyzed using generalized linear models. RESULTS: The RNFLT was significantly higher in patients with uveitis (p < .001). Active uveitis patients had a thicker RNFL than the controls and the patients with quiescent uveitis (p < .001). Anterior uveitis was associated with thinner RNFL in global and inferotemporal quadrant (p = .011 and 0.013, respectively). Thickening of RNFL was associated with posterior uveitis and Behçet's disease in all quadrants (p < .001) and idiopathic uveitis in the superonasal and nasal quadrants (p = .001). CONCLUSION: Active uveitis, as well as posterior uveitis and Behcet's disease-associated uveitis, is a major confounding factor in RNFL analysis and therefore detection of glaucoma.