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.

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.

Macular injury resulting from a high-powered tank laser telemetry device.

A high-powered laser is an essential part of a modern military rangefinder; however, this paper presents three cases with macular injury resulting from a high-powered tank laser telemetry device. All injuries occurred when another user deliberately pointed the telemetry target unit at the patient's eyes. The devastating effect of this high-powered laser resulted in a permanent foveal scar in the second patient and a macular hole formation in the third patient. This report emphasises that education plays a primary role in preventing accidental laser injuries. Using general guidelines and safety regulations will prevent accidental macular injuries.

Soccer ball related posterior segment closed-globe injuries in outdoor amateur players.

BACKGROUND: The aim of this study is to report the characteristics, treatment, and anatomical and functional outcomes of outdoor amateur soccer players with soccer ball-related posterior segment ocular trauma. METHODS: We conducted a retrospective chart review of 22 patients with diagnoses of closed-globe ocular trauma caused by soccer play activity from 2004 through 2008. Injuries were classified according to Ocular Trauma Classification. RESULTS: All patients (n=22) were male, and all injuries were caused by contact with the soccer ball itself. Sixteen (72%) patients did not require any treatment. Surgery was performed on 5 (22%) patients. Twenty (91%) patients had 5/200 or better visual acuity (VA) at presentation and 2 (9%) had hand movements or worse VA. At the final visit, all patients had 5/200 or better VA (p<0.01). CONCLUSION: A soccer ball can cause significant posterior segment trauma, and using eye protection equipment might be an appropriate solution.

Ocular injuries caused by metal caps of carbonated mineral water bottles.

BACKGROUND: Bottles containing carbonated drinks are potentially hazardous to the eye. In this study, we aimed to document the clinical characteristics and visual outcomes in a series of patients with ocular injury from flying metal caps of carbonated mineral water bottles. METHODS: Retrospective review of ocular injuries due to metal caps of carbonated mineral water bottles. RESULTS: Sixteen eyes of sixteen patients were included in the study. All of the patients were male, with a mean age of 24 years. Ten of the patients had a history of using improper tools for bottle cap removal. The left eye was involved in twelve cases and the right eye in four cases. All patients had contusion-type closed-globe injury. Varying degrees of hyphema were observed in all patients, and vitreous hemorrhage was present in four. The visual acuity at the last follow-up was 20/20 in 15 of the patients. CONCLUSION: The use of a bottle cap opener is essential for preventing ocular damage from pressed metal caps of carbonated drinks. In addition to popularising the use of screw cap bottles, warning labels that alert consumers about the possibility of eye injury should be placed on carbonated drinks with pressed metal caps.

Evaluation of retina and choroid perfusion with optical coherence tomography angiography in patients with retinitis pigmentosa.

PURPOSE: In this study, we aimed to evaluate macular perfusion with optical coherence tomography angiography (OCTA) and to investigate the correlation between OCTA quantitative data and visual acuity (VA) in patients with retinitis pigmentosa (RP). METHODS: This retrospective single-center study was conducted on 60 eyes of 30 RP patients and 52 healthy eyes. The vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of the macula, the size of foveal avascular zone (FAZ), choriocapillary flow density (FD) were measured using OCTA. Quantitative data obtained with OCTA were compared between the two groups. In addition, the correlation between the OCTA measurements and VA was examined. RESULTS: In patients with RP, the choriocapillary FD was decreased (p = 0.001), the FAZ area was enlarged (p = 0.010), and the VDs of the SCP and DCP were decreased in all areas (p = 0.001). Correlation was found between VA and SCP VD, whole image (p = 0.011, rho = -0.327) and parafoveal (p = 0.001, rho = -0.444) areas. CONCLUSION: Quantitative data from OCTA showed reduced macular perfusion in patients with RP compared to healthy controls. There was also a correlation between the quantitative OCTA data and VA.

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.

Optical Coherence Tomography Angiography in Patients with Cone Dystrophy.

PURPOSE: This study aimed to evaluate macular perfusion using optical coherence tomography angiography (OCTA) in patients with cone dystrophy and to determine the associations between the quantitative data of OCTA and functional parameters. METHODS: The data of 36 eyes of 18 patients with cone dystrophy and 38 eyes of 19 healthy controls were analyzed. The superficial and deep capillary plexus (SCP and DCP) vessel densities (VD) of the macula, the foveal avascular zone (FAZ) and choriocapillary flow density values were obtained using OCTA. The associations between visual acuity (VA) and full-field electroretinography (ffERG) and the quantitative data of OCTA, and the associations between OCTA and ffERG were analyzed. RESULTS: : VD was significantly lower in all areas except the foveal area in SCP in the cone dystrophy group compared to the control group. VA was found to be associated with the VDs of the SCP and DCP except for that of the foveal SCP. VA was also associated with dark-adapted, light-adapted wave amplitudes. CONCLUSION: OCTA quantitatively showed that macular perfusion was decreased in cone dystrophy compared to the healthy controls. In addition, there was an association between VA and ffERG parameters and quantitative data of OCTA.

Ocular Complications of Intravesicular BCG Treatment for Bladder Carcinoma.

PURPOSE: To report genital and ocular Bacillus Calmette-Guérin (BCG) infection as a rare complication of intravesical BCG immunotherapy. METHODS: We report a patient with bladder carcinoma who developed penile and ocular BCG infection. Medical history, clinical features, imaging findings, histopathological evaluation, and response to treatment clinched the diagnosis. RESULT: Granulomatous inflammation was noted on histopathological evaluation of lung and cutaneous lesion of the penis. The left eye with choroidal tubercle and tractional retinal detachment involving fovea underwent pars plana vitrectomy. After silicone removal, best-corrected visual acuity was 20/100 and patient received anti-TB regimen for 12 months. At 1 year follow-up, the choroidal tuberculoma was found to have completely resolved and the ocular status was stable. CONCLUSIONS: Though there are other reported cases of BCG infection secondary to intravesical BCG instillation noted in the literature, penile granuloma accompanying with choroidal tubercle is an uncommon form among these complications.

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.

Evaluation of the relationship of lymphangiogenesis markers with disease pathogenesis in patients with Behçet's uveitis.

OBJECTIVES: The present study aims to evaluate the relationship between Behçet's uveitis and lymphangiogenesis by determining levels of Vascular endothelial growth factor-C (VEGF-C, its receptors sVEGFR-2, sVEGFR-3 and lymphangiogenesis markers podoplanin (PDPN) and lymphatic vessel endothelial hyaluronan receptor 1(LYVE-1), and C-type lectin domain family 1 member B (CLEC2). MATERIALS AND METHODS: 55 patients with BD uveitis and 31 healthy control subjects were enrolled in the study. RESULTS: sVEGFR-2, sVEGFR-3, VEGF-C/sVEGFR-2 ratio, PDPN and LYVE-1 levels were higher in the patient group. A positive correlation was found between LYVE-1 and hsCRP levels. PDPN had a strong predictive value for progression with a cut-off value of 2 pg/mL, with 69% sensitivity and 68% specificity (p = 0.001). CONCLUSION: LYVE-1 and PDPN can be good representatives of the ongoing inflammatory processes in BD uveitis and point out that the disease can be related to lymphangiogenesis.

Determination of serum vascular endothelial growth factor (VEGF) and VEGF receptor levels with VEGF gene polymorphisms in patients with Behçet's uveitis.

BACKGROUND: Behçet's disease (BD) is a chronic inflammatory vasculitis affecting multiple organs. Uveitis is frequently seen in patients with BD, especially in Turkish population. OBJECTIVES: To investigate vascular endothelial growth factor (VEGF) gene polymorphisms along with the levels of VEGF and VEGF receptors in patients with Behçet's uveitis (BU). MATERIAL AND METHODS: Fifty-five BD-associated uveitis patients and 30 ageand sex-matched controls were included in this case-control study. The genotypes of the single nucleotide poymorphisms (SNPs): rs2010963 (+405G), rs3025039 (+936T) and rs699947 (-2598A) of the VEGF-A gene were determined using real-time polymerase chain reaction (RT-PCR) and serum levels of VEGF and VEGF receptors were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: No associations of the VEGF gene polymorphisms were observed in BD uveitis patients, but arthritis was present in 53.3% of patients not possessing CT genotype in C3025039→T polymorphism (p = 0.024). Although there were no statistically significant differences in serum VEGF-A, VEGF-C and soluble vascular endothelial growth factor receptor-3 (sVEGFR-3) levels (p < 0.05), serum vascular endothelial growth factor receptor-1 (VEGFR-1) and sVEGFR-3 levels were significantly higher in the BD group (p < 0.001 and p = 0.001, respectively). In addition, VEGF-C/soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) ratio was significantly higher (p < 0.001), while VEGF-A/VEGFR-1 and VEGF-C/sVEGFR-3 ratios were significantly lower (p < 0.001 and p = 0.033, respectively) in BD patients compared to controls. Also, VEGF-C/sVEGFR-3 (p = 0.024, r = 0.37) and VEGF-C/sVEGFR-2 (p = 0.020, r = 0.38) ratios were positively correlated with disease duration. CONCLUSIONS: The significant changes in sVEGFR-3 levels and VEGF-C/sVEGFR-3 ratio has shown that lymphangiogenesis processes might take place in the pathogenesis of BD uveitis, and these parameters can be important indicators of evaluation of BD patients with uveitis together with disease duration.

Pars plana vitrectomy timing in deadly weapon-related open-globe injuries.

OBJECTIVES: The objective of this study is to evaluate the effect of vitrectomy timing on anatomical and functional outcomes in cases with open-globe injuries caused by improvised explosive devices (IEDs). METHODS: A retrospective review of ocular injuries caused by IEDs was undertaken. The eyes were classified into four groups based on the timing of vitrectomy: early (Group-1; 2-4 days), delayed (Group-2; 5-7 days), late (Group-3; 8-14 days) and very late (Group-4; >14 days). RESULTS: The medical records of 351 patients were reviewed, and 212 patients were excluded. A total of 189 eyes of the remaining 139 patients were analysed. Visual improvements were statistically significant compared to the baseline values in all groups (p < 0.001). The early group showed better functional and structural outcomes when compared to the other groups. There was also no proliferative vitreoretinopathy (PVR) in the early group, while PVR was at the highest rate (25%) in the very late group and constituted the most significant reason for recurrent retinal detachment. CONCLUSION: Both functional and anatomical outcomes were better in the early group. Delayed surgery may be indicated for some cases, but 1-week interval seems to be an optimal time-frame in open globe injuries due to IEDs.

Effect of blunt ocular trauma on retinal microvasculature: An optical coherence tomography angiography study.

BACKGROUND: To evaluate the retinal vascular changes and foveal avascular zone area in patients with unilateral blunt ocular trauma using optical coherence tomography angiography. METHODS: This retrospective study consisted of 50 traumatized and 50 contralateral sound eyes of the patients with blunt ocular trauma. The foveal avascular zone area, choriocapillaris flow area, foveal, parafoveal, and perifoveal vessel densities in both superficial capillary plexus and deep capillary plexus and central macular thickness were evaluated. RESULTS: There were no significant differences between traumatized and sound eyes in the foveal avascular zone area (p:0.36), choriocapillaris flow area (p:0.43), central macular thickness (p:0.67), and in vessel densities of superficial capillary plexus over all regions (p > 0.05 for all). However, the vessel densities of deep capillary plexus were significantly lower in traumatized eyes (p < 0.05 for all). CONCLUSION: Optical coherence tomography angiography demonstrated a significant decrease in retinal deep capillary plexus vessel density of the eyes effected by blunt ocular trauma, even with no evident findings on fundus examination or structural spectral domain-optical coherence tomography changes.