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 status of the choroid in patients with optic disc drusen.

PURPOSE: To investigate the subfoveal and peripapillary choroidal thickness (CT) and the choroidal vascularity index (CVI) in patients with optic disc drusen (ODD). METHODS: This cross-sectional study examined the eyes of 17 patients with ODD and 18 healthy control subjects. The CT values were calculated manually from the images captured by enhanced depth imaging-optical coherence tomography (EDI-OCT). The CVI was defined as the proportion of the vascular area to the total choroidal area at the subfoveal and peripapillary areas after binarization of the EDI-OCT images. RESULTS: It was found that the mean subfoveal CVI value in the ODD group was significantly lower than that in the control group (p = 0.006). The mean peripapillary CVI values were significantly lower in all of the quadrants in the ODD group when compared with the control group (p = 0.008 for the temporal quadrant, p = 0.014 for the nasal quadrant, p = 0.024 for the superior quadrant, and p = 0.038 for the inferior quadrant). Regarding the CT, there were no significant differences in the subfoveal and peripapillary CT values between the ODD group and the control group (p >  0.05 for all values). CONCLUSION: The findings of this study indicate ODD to be associated with decreased subfoveal and peripapillary CVI, even though the subfoveal and peripapillary CT values were within the normal range. This result may prove important in relation to identifying a choroidal vascular network that appears to be morphologically normal but microstructurally impaired due to ODD. Further studies are required to verify the significance of CVI in the pathogenesis and complications of ODD.

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.

Vitreous levels of vascular endothelial growth factor, stromal cell-derived factor-1α, and angiopoietin-like protein 2 in patients with active proliferative diabetic retinopathy.

PURPOSE: To determine the vitreous levels of vascular endothelial growth factor (VEGF), stromal cell-derived factor-1α (SDF-1α) and angiopoietin-like protein 2 (ANGPTL2) in patients with active proliferative diabetic retinopathy (PDR), and to ascertain their contribution on different clinical presentation of active PDR. METHODS: This case-control study included 31 eyes with active PDR and 10 eyes with idiopathic macular hole (MH) (control group). Eyes with active PDR were divided into three subgroups: vitreous hemorrhage (VH), tractional retinal detachment (TRD) caused by active fibrovascular membrane (FVM), and coexistence of VH and TRD with FVM. Vitreous samples obtained during vitrectomy were analyzed for concentrations of VEGF, SDF-1α, and ANGPTL2. RESULTS: Vitreous level of VEGF (2021 (168-6550) pg/ml vs 110.1 (74.5-236) pg/ml), SDF-1α (517 (194-1044) pg/ml vs 388 (320-535) pg/ml), and ANGPTL2 (725 (131-1590) ng/ml vs 196 (75.9-437) ng/ml) were significantly higher in eyes with active PDR than in control group (p < 0.001, p = 0.002, and p < 0.001, respectively). The concentrations of these meaditors in each active PDR subgroups were also significantly higher than control group (p < 0.05). The vitreous level of ANGPTL2 was significantly higher in eyes with TRD caused by FVM (1033 ± 401 ng/ml) than in eyes with VH (561 ± 237 ng/ml; p = 0.008). CONCLUSION: High levels of SDF-1α, ANGPTL2 and particularly VEGF seem to be associated with PDR. Since the vitreous levels of ANGPTL2 tend to be higher in eyes with active fibrovascular tractional detachment, vitreous levels of this chemokine seem to be affected by the clinical presentation of vascularly active PDR eyes.

Evaluation of radial peripapillary capillary density in patients with Fuchs uveitis syndrome.

PURPOSE: To quantitatively analyze the microcirculation in the peripapillary sectors in the affected eyes and fellow unaffected eyes of individuals with unilateral Fuchs uveitis syndrome (FUS) using optical coherence tomography angiography (OCTA), and to compare the radial peripapillary capillary vessel density (RPCvd) with normal and age-matched individuals. METHODS: Eyes were divided into three groups based on the involvement of the FUS: FUS-positive eye of patients (study eye), fellow eye of FUS-positive patients (fellow eye), and the control eye for the control group (control eye). RPCvd (%) and peripapillary retinal nerve fiber layer (RNFL) thickness (µm) at eight equal sectors and two equal hemispheres were automatically calculated in peripapillary region via OCTA. RESULTS: This study included 105 eyes of 71 patients: 34 FUS-positive eyes of 34 patients, 34 fellow eyes of FUS-positive patients, and 37 control eyes of 37 patients. RPCvd was significantly lower in study eyes than in fellow and control eyes in the peripapillary region (p = 0.044 and p = 0.005, respectively). There was no significant difference between fellow eyes and control eyes regarding RPCvd in any region (p > 0.05 for all). There were no significant differences between the three groups regarding peripapillary RNFL values (p > 0.05 for all). CONCLUSION: OCTA is a novel technology for imaging of the RPC network in patients with FUS. Lower radial peripapillary capillary vessel density in FUS could induce capillary insufficiency and impairment of ocular blood flow to optic nerve head.

The ultrastructural alterations in the lens capsule and epithelium in eyes with traumatic white cataract.

PURPOSE: To demonstrate the morphological and physiological characteristics of lens epithelial cells (LECs) in patients with traumatic cataract using transmission electron microscopy (TEM) to further understand penetrating ocular injury-induced cataract morphology and epithelial repair mechanisms involved at a cellular level. METHODS: This is a prospective international study. Sixteen eyes of 16 consecutive patients who were diagnosed as traumatic white cataracts following the anterior lens capsule perforation and 13 eyes of 13 patients with idiopathic posterior subcapsular cataract were included to the study. The anterior lens capsules (aLCs: basement membrane and associated LECs) were obtained from cataract surgery and prepared for TEM. RESULTS: Two prominent cell types were observed in all aLCs of the traumatic cases: degenerated type LECs having variable sized intraepithelial vacuoles close to injury site and normal appearing LECs having an euchromatic nucleus distant from the injury site. In control group, the LECs and all their elements were in normal ultrastructural pattern except some small intraepithelial vacuoles, which were fewer and smaller than the vacuoles in the degenerated LECs of the traumatic group. CONCLUSIONS: The ultrastructural findings of our cases support that traumatically induced dysfunction of the lens epithelium may lead to an edema in superficial cortical lens fibers that subsequently undergo degeneration and produce a localized zone of vacuolization.

Electron microscopic evaluation of anterior lens epithelium in patients with idiopathic congenital cataract.

PURPOSE: To investigate the ultrastructure of the lens epithelial cells (LECs) in patients with idiopathic congenital cataract. METHODS: This is a prospective interventional study. The anterior lens capsules (aLC: basement membrane and associated LECs) were taken from 16 eyes of 12 consecutive patients who were diagnosed as having idiopathic congenital cataracts. The aLCs were obtained from cataract surgery and prepared for transmission electron microscopy (TEM). RESULTS: Some significant ultrastructural changes were observed in all aLCs of the participants. The anterior LECs showed alterations in different areas which were partly cuboidal and partly squamous in shape. The LECs had euchromatic nucleus and included some vacuoles in the cytoplasms as a remarkable alteration. The sizes of these intraepithelial cell vacuoles were changeable. CONCLUSIONS: We identified remarkable changes in LECs of the eyes with idiopathic congenital cataract by TEM. It can be assumed that oxidative damage may be associated with these ultrastructural changes in LECs of the eyes with idiopathic congenital cataracts.

A histopathological investigation of Tenon's capsule in diabetic eyes.

The aim of this study is to investigate the histopathological features of Tenon's capsule in eyes with diabetic macular oedema and to compare them between diabetic eyes and healthy subjects. The study included 26 eyes with diabetic oedema and 17 healthy eyes as healthy controls. Tenon's capsule biopsy specimens were processed with the routine electron microscopic analysis technique. Type I and III collagen fibres were labelled immunohistochemically to determine the amounts of predominating collagen fibres. Leica Q-Win program was used to calculate the amounts of collagen fibres type I and type III and independent-t test was utilized to compare the obtained results between the groups. Statistical significance was set at p < 0.05. Demographic characteristics of both groups were similar (p > 0.05). Collagen type I and type III immunoreactivity was observed both in the control and the diabetic groups. The Amounts of collagen fibres type I and type III were significantly higher in the diabetic group than in the control group (mean collagen type I area: 13.410 ± 0.99 and mean collagen type III area: 23.692 ± 0.17 in the control group; mean collagen type I area: 25.270 ± 6.48 and mean collagen type III area: 28.192 ± 0.82 in the diabetic group. p = 0.0037 for type I and p = 0.0000 for type III). In light of the findings of this study, it can be assumed that diabetes mellitus may engender increased amounts of collagen in Tenon's capsule. This alteration affecting the success of filtration surgery should be kept in mind especially in diabetic eyes with glaucoma.

Quantitative evaluation of retinal and choroidal microcirculation in inactive ocular sarcoidosis.

Purpose: To evaluate retinal and choroidal alterations in eyes with inactive ocular sarcoidosis and to compare the findings with healthy controls. Methods: This cross-sectional study included 11 patients with inactive ocular sarcoidosis (study group) and 11 healthy individuals (control group). Retinal and choroidal vascular differences were evaluated using optical coherence tomography angiography (OCTA) and enhanced depth imaging-optical coherence tomography (EDI-OCT). Results: A total of 21 eyes of ocular sarcoidosis patients without active inflammation and 22 eyes of healthy controls were analyzed. The mean whole-image deep capillary plexus vessel density was significantly lower in the study group than in the control group (P = 0.03). The acircularity index values were significantly higher, and the foveal density-300 values were significantly lower in the study group than in the control group (P = 0.01, both). The flow areas of the choriocapillaris at 1-, 2-, and 3-mm radius areas were also significantly lower in the study group (all P < 0.01). The mean choroidal thickness (CT) was significantly lower in all regions between nasal and temporal at 3000 µm in the study group (all P < 0.05). The choroidal vascularity index (CVI) values were also significantly lower in the study group (P < 0.01). Conclusion: Ocular sarcoidosis was associated with a reduction in CT and the CVI with a decrease in retinal vessel density and choriocapillary flow parameters. The combination of OCTA and EDI-OCT imaging may be useful in monitoring ocular sarcoidosis eyes to detect alterations in the retinal and choroidal layers.

Aqueous Humor Levels of Vascular Endothelial Growth Factor and Stromal Cell-Derived Factor-1α in Age-Related Macular Degeneration.

OBJECTIVES: This study investigated the contribution of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) angiogenic mediators in eyes with age-related macular degeneration (AMD). METHODS: Aqueous humor specimens taken during cataract surgery in 7 cases of intermediate stage (nonexudative) AMD and 7 cases of late stage (exudative) AMD were evaluated using chemiluminescent immunoassay testing in this prospective case-control study. Mediator levels were compared with the normal reference values of 7 patients without any disease other than cataract. RESULTS: The groups were similar in terms of age and gender (p>0.05). The aqueous humor levels of VEGF in both the intermediate AMD (median: 224.3 pg/mL, range: 44.8-380.4 pg/mL) and late-stage AMD (median: 108.7 pg/mL, range: 61.9-223.5 pg/mL) patients were similar to those of the control group (median: 121.1 pg/mL, range: 24.9-156.6 pg/mL) (p=0.256). Moreover, there was no significant difference in the SDF-1α concentrations between the intermediate AMD (median: 160.9 pg/mL, range 130-166.3 pg/mL), late AMD (median: 161 pg/mL, range: 154.1.9-171.6 pg/mL), and control group values (median: 161 pg/mL, range: 155.2-219 pg/mL) (p=0.763). CONCLUSION: The aqueous humor levels of VEGF and SDF-1α were within the normal range in patients with intermediate and late-stage AMD.

UNCOMPLICATED PACHYCHOROID IN RELATION TO OBSESSIVE-COMPULSIVE DISORDER: AN OCT-ANGIOGRAPHY STUDY.

BACKGROUND: The aim of this study was to evaluate potential changes in choroidal flow in patients with newly diagnosed obsessive-compulsive disorder based on optical coherence tomography angiography findings and to investigate the relationship between subfoveal choroidal thickness and choriocapillaris flow area. METHODS: This prospective study included newly diagnosed obsessive-compulsive disorder patients and healthy controls. All patients underwent enhanced depth imaging-optical coherence tomography imaging to assess the subfoveal choroidal thickness and optical coherence tomography angiography imaging to evaluate the choriocapillaris flow area. RESULTS: A total of 55 patients with obsessive-compulsive disorder and 50 controls were included. The mean subfoveal choroidal thickness was significantly greater in the obsessive-compulsive disorder group compared to the control group (p˂0.001). Regarding the choriocapillaris flow area, the values for area with a radius of 1 mm, 2 mm and 3 mm were significantly lower in the obsessive-compulsive disorder group than in the control group (p=0.019, p=0.014, and p=0.004, respectively). There was a significant negative correlation between subfoveal choroidal thickness and choriocapillaris flow area with a radius of 1mm (r=-0.387, p=0.024). CONCLUSION: Choroidal changes in obsessive-compulsive disorder patients suggest the choroidal features of uncomplicated pachychoroid. Obsessive-compulsive disorder may be prone to a spectrum of conditions characterized by pachychoroid features.

A case of adult-onset tubulointerstitial nephritis and uveitis syndrome presenting with granulomatous panuveitis.

The tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disorder that is probably underdiagnosed in clinical practice. Ocular involvement in TINU syndrome not only presents with the nongranulomatous anterior uveitis in 80% of patients but also manifests as intermediate, posterior, or panuveitis. This case report mentions an adult male patient who presented with granulomatous iridocyclitis with panuveitis and mild renal insufficiency. Workup for connective tissue and infectious diseases was negative for the patient. He was diagnosed with TINU syndrome based on the findings of renal biopsy. Both the uveitis and nephritis promptly responded well to steroid treatment, and there was no recurrence during the follow-up of 24 months.

Effects of Fuchs uveitis syndrome on the ultrastructure of the anterior lens epithelium: A transmission electron microscopic study.

PURPOSE: The purpose of the study was to investigate the electron microscopic findings of the lens epithelial cells (LECs) in patients with Fuchs uveitis syndrome (FUS) who suffered from cataracts and to compare those with age-matched controls. METHODS: This study was a prospective, comparative case series. The anterior lens capsules (ALC: basement membrane and associated LECs) were taken from 12 eyes of 12 cases of FUS and ten eyes of ten control patients. The ALCs were obtained from cataract surgery and prepared for transmission electron microscopy (TEM). RESULTS: There were no statistically significant differences regarding the age or gender between the FUS group and the control group (P > 0.05). In the TEM examinations of the ALCs, all of the FUS cases revealed similar significant ultrastructural changes when compared to the control patients. In the FUS group, the LECs showed homogeneous thickening and irregularity which included some small vacuoles in different areas of the epithelial tissue. Moreover, in some areas of the LECs, widespread, oval-shaped, pigment clusters were detected. Conversely, in the control group, the LECs and all of their elements were in normal ultrastructural patterns, with the exception of some small intraepithelial vacuoles which were fewer and smaller than those in the FUS group. CONCLUSION: Ultrastructural analysis of the ALC of the patients with FUS disclosed some significant alterations which may be related to the summation of oxidative stress, intraocular inflammation, and iris atrophy.