FOVEAL MÜLLER CELL CONE AS A PROGNOSTIC OPTICAL COHERENCE TOMOGRAPHY BIOMARKER FOR INITIAL RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN CYSTOID DIABETIC MACULAR EDEMA.

PURPOSE: To investigate the effect of the foveal Müller cell cone structure on the anatomical and functional response to intravitreal bevacizumab treatment in patients with diabetic macular edema. METHODS: In 93 treatment-naive eyes with center-involved cystic type diabetic macular edema, spectral-domain optical coherence tomography scans of baseline were retrospectively evaluated to determine the foveal Müller cell cone structure and prognostic features including length of disorganization in the retinal inner layers and ellipsoid zone disruption. The area and circularity of the foveal avascular zone of the superficial and deep capillary plexus 1 month after intravitreal bevacizumab treatment were evaluated using optical coherence tomography angiography. RESULTS: Destruction of the foveal Müller cell cone structure and a large foveal avascular zone in the deep capillary plexus (mm2) correlated strongly with a poor anatomical response (CST > 250 µm) at 1 month after first intravitreal bevacizumab (Exp [B] = 29.444, P = 0.002 and Exp [B] = 12.419, P = 0.013, respectively). A destroyed Müller cell cone structure (P = 0.008) and length of ellipsoid zone disruption (P < 0.001) at baseline were associated with poor visual acuity at 1 month after the first intravitreal bevacizumab. CONCLUSION: The foveal Müller cell cone structure correlates with the response to initial antivascular endothelial growth factor treatment.

Structural and Functional Characterization of the Retinal Effects of Hydroxychloroquine Treatment in Healthy Eyes.

PURPOSE: To evaluate the influence of hydroxychloroquine in visual field and retinal layer thickness. METHODS: This is a retrospective cross-sectional study. Patients taking hydroxychloroquine without signs of hydroxychloroquine retinopathy were included. Optical coherence tomography segmentation was used to obtain the ETDRS map thickness of each retinal layer. Groups were divided into short-term (< 5 years) and long-term (≥5 years) drug use. RESULTS: We included 93 eyes of 93 patients (short-term: 25 eyes; long-term: 68 eyes). The inner nuclear layer (INL) was thinner in the long-term group (32.86 ± 2.12 vs. 34.14 ± 2.37 µm; p = 0.014). Considering long-term cases, the parafoveal ganglion cell layer (GCL) showed an inverse correlation with cumulative dose (r = -0.37; p < 0.001). After adjusting for confounders, parafoveal ganglion cell complex thickness was associated with cumulative dose (ß = -0.239; p = 0.011). The parafoveal outer retina and visual field indices were similar between groups and did not correlate with cumulative dose. CONCLUSION: Hydroxychloroquine leads to progressive thinning of the parafoveal inner retina, particularly the INL and GCL. Visual field indices do not reflect the long-term effects of the drug.

Perifoveal interdigitation zone loss in hydroxychloroquine toxicity leads to subclinical bull's eye lesion appearance on near-infrared reflectance imaging.

PURPOSE: To characterize the ultrastructural and functional correlates of hydroxychloroquine (HCQ)-induced subclinical bull's eye lesion seen on near-infrared reflectance (NIR) imaging. METHODS: An asymptomatic 54-year-old male taking HCQ presented with paracentral ring-like scotoma, abnormal multifocal electroretinography (mfERG) and preserved ellipsoid zone on optical coherence tomography (OCT). Dense raster OCT was performed to create en face reflectivity maps of the interdigitation zone. Macular Integrity Assessment (MAIA) microperimetry and mfERG findings were compared with NIR imaging, en face OCT, retinal thickness profiles and wave-guiding cone density maps derived from flood-illumination adaptive optics (AO) retinal photography. RESULTS: The bull's eye lesion is an oval annular zone of increased reflectivity on NIR with an outer diameter of 1450 µm. This region corresponds exactly to an area of preserved interdigitation zone reflectivity in en face OCT images and of normal cone density on AO imaging. Immediately surrounding the bull's eye lesion is an annular zone (3°-12° eccentricity) of depressed retinal sensitivity on MAIA and reduced amplitude density on mfERG. Wave-guiding cone density at 2° temporal was 25,400 per mm2. This declined rapidly to 12,900 and 1200 per mm2 at 3° and 4°. CONCLUSION: Multimodal imaging illustrated pathology in the area surrounding the NIR bull's eye, characterized by reduced reflectance, wave-guiding cone density and retinal function. Further studies are required to investigate whether the bull's eye on NIR imaging and en face OCT is prominent or consistent enough for diagnostic use.

BETTER PROGNOSIS FOR EYES WITH PRESERVED FOVEAL DEPRESSION AFTER INTRAVITREAL RANIBIZUMAB INJECTION FOR MACULAR EDEMA SECONDARY TO CENTRAL RETINAL VEIN OCCLUSION.

PURPOSE: To determine the prognosis of eyes with central retinal vein occlusion that had a preserved foveal depression at the baseline and were treated by intravitreal ranibizumab injections (IRIs). METHODS: The authors reviewed the medical records of 23 eyes of 23 consecutive treatment-naive patients who received IRIs to treat the macular edema due to central retinal vein occlusion. Eyes were classified by the pre-IRI presence or absence of a foveal depression. A foveal depression was defined as a central foveal thickness that was <50 µm thinner than the average thickness at 200 µm temporal and nasal to the central fovea. The characteristics of the two groups were compared. RESULTS: Seven of 23 eyes had a preserved foveal depression before the IRI. The mean number of injections within 12 months after the initial IRI was significantly fewer (P < 0.001) in eyes with foveal depression (1.6 ± 0.5) than in eyes without foveal depression (4.3 ± 1.3). The mean best-corrected visual acuity at 12 months after the initial IRI was significantly better (P = 0.003) in eyes with foveal depression (0.10 ± 0.17 logarithm of the minimum angle of resolution [logMAR] units; 20/25 Snellen units) than in eyes without foveal depression (0.77 ± 0.54 logMAR units; 20/118 Snellen units). CONCLUSION: These results indicate that the prognosis is better for eyes with a foveal depression before the IRI treatment for a macular edema secondary to central retinal vein occlusion.

TWENTY-FOUR MONTH FOLLOW-UP OF TOCILIZUMAB THERAPY FOR REFRACTORY UVEITIS-RELATED MACULAR EDEMA.

BACKGROUND: To report the 24-month efficacy and safety of the interleukin-6 receptor antagonist tocilizumab (TCZ) for refractory uveitis-related macular edema (ME). METHODS: Data were obtained by standardized chart review. Patients with quiescent uveitis seen at a single tertiary referral center, for whom ME was the principal cause of reduced visual acuity. OUTCOME MEASURES: Central foveal thickness measured by optical coherence tomography; degree of anterior and posterior chamber; inflammation (Standardization of Uveitis Nomenclature Working Group criteria); and visual acuity (Snellen and logarithm of the minimum angle of resolution) were recorded in all patients during TCZ therapy at months 1, 3, 6, 12, 18, and 24. RESULTS: Sixteen eyes from 12 patients (10 women) were included. Mean age was 34.6 years. Mean duration of ME was 13.2 years. All patients achieved 24 months of follow-up and that is the census date for data collection. Before TCZ was commenced, ME was present, and all patients had been previously treated with immunosuppressive therapy and biologic agents. Uveitis diagnoses were juvenile idiopathic arthritis associated, uveitis (n = 6), birdshot chorioretinopathy (n = 2), idiopathic panuveitis (n = 2), sympathetic ophthalmia (n = 1), and ankylosing spondylitis (n = 1). Mean central foveal thickness (95%; confidence interval) was 516 ± 55 µm at baseline, improving to 274 ± 13 at Month 12 (P = 0.0004), and sustained at 274 ± 14 at Month 24 of follow-up (P = 0.00039). Mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.78 ± 0.18 (Snellen 20/120 ± 20/30) at baseline to 0.42 ± 0.17 (20/52 ± 20/30) at Month 12 (P = 0.0001) and 0.40 ± 0.17 (20/50 ± 20/30) at Month 24 of follow-up (P = 0.0002). Tocilizumab therapy was withdrawn in 5 patients with sustained remission at Month 12 but in all, ME relapsed between 1 and 3 months after TCZ discontinuation. Rechallenge of TCZ infusions led to recovery of uveitis control and ME resolution. Two adverse events were reported during two 4-month follow-ups: one Grade 1 neutropenia and one community-acquired pneumonia. CONCLUSION: In this long-term study, TCZ was effective and had a comparable safety profile to published data for TCZ use in other indications, when used for the treatment of refractory uveitis-related ME.

Management of Subfoveal Perfluorocarbon Liquid: A Review.

Perfluorocarbon liquid (PFCL) has been widely used in vitreoretinal surgeries, especially in retinal detachment treatment. A prominent complication of intraoperative PFCL application is inadvertent subretinal PFCL retention. Subfoveal PFCL, even in small amounts, receives much attention due to its potential side effect on the macular structure and function. Whether to observe with follow-up or to deal with surgery is often an intractable problem in the management of subfoveal PFCL. Safety and necessity are the 2 key issues in considering surgical treatment, that is, can we avoid surgically induced macular injury and will surgery be beneficial for the recovery of vision? Herein, the authors review sub-foveal PFCL retention with its risk factors, morphological manifestations, pathological studies, clinical natural consequences, and different surgical methods with their outcomes. Analysis of the existing literature shows that visual acuity improved significantly after subfoveal PFCL removal or displacement and was positively correlated with visual acuity before the operation.

EFFECT OF INTRAVITREAL RANIBIZUMAB ON GANGLION CELL COMPLEX AND PERIPAPILLARY RETINAL NERVE FIBER LAYER IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To analyze the changes in ganglion cell complex and peripapillary retinal nerve fiber layer thickness, in central macular thickness and choroidal thickness on spectral domain optical coherence tomography in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. METHODS: All consecutive patients with untreated neovascular age-related macular degeneration received loading phase of three monthly intravitreal ranibizumab, followed by retreatments on a pro re nata protocol for 12 months. PRIMARY OUTCOME: changes in ganglion cell complex and retinal nerve fiber layer at the end of follow-up. Secondary outcome: changes in best-corrected visual acuity, central macular thickness, and choroidal thickness at the end of follow-up. Choroidal thickness was measured at 500 µm, 1000 µm, and 1,500 µm intervals nasally, temporally, superiorly, and inferiorly to the fovea, respectively, on horizontal and vertical line scans centered on the fovea. RESULTS: Twenty-four eyes were included. Ganglion cell complex and peripapillary retinal nerve fiber layer thickness did not show statistically significant changes through 12 months (55.6 ± 18.5 and 81.9 ± 9.9 µm at baseline, 52.7 ± 19.3 and 84.6 ± 15.5 µm at month 12, P > 0.05). Central macular thickness showed progressive decrease from baseline to month 12, with maximum reduction at month 3 (P < 0.001). Statistically significant reduction in choroidal thickness was registered in the nasal 500, 1000, and 1,500 µm from the fovea, corresponding to the papillomacular region (from 169.6 ± 45.3 to 153.9 ± 46.9, P < 0.001). CONCLUSION: Intravitreal ranibizumab injections did not affect retinal nerve fiber layer and ganglion cell complex thickness in 1-year follow-up. Choroidal thickness in papillomacular area and central macular thickness was significantly reduced at the end of treatment. Further studies, with larger sample, longer follow-up, and greater number of injections, are warranted.

Effect of nepafenac on the foveal profile of glaucomatous patients undergoing phacoemulsification.

PURPOSE: Retrospective, pilot study to determine whether nepafenac treatment pre- and postcataract surgery in glaucoma patients using topical hypotensive agents minimized cystoid macular edema by comparing pre- and postsurgical foveal characteristics, as in some cases these agents cannot be withdrawn and, hypothetically, their inflammatory effect on the fovea could be neutralized by the addition of nepafenac. METHODS: Patients were divided into two subgroups depending on whether or not topical nepafenac was added to the surgical protocol (NEP = nepafenac group and nNEP = non nepafenac group). All had undergone phacoemulsification and data on pre- and postoperative macular status were recorded. RESULTS: In the nNEP group, there was a significant increase in foveal thickness (FT) in the first month postoperative visit with respect to the preoperative status (p = 0.006), and this situation did not change at the third postoperative month (p = 0.9411). In the NEP group, the increase in FT was not significant at the first month after surgery (p = 0.056) nor at the final visit (p = 0.268), in contrast to the nNEP group. CONCLUSION: This study of the possible prophylactic effect of nepafenac on postoperative macular edema supports the results of other studies that confirm subclinical edema post phacoemulsification, and found a significantly lower gradient in the increase in FT in patients treated pre- and postoperatively with nepafenac.

[Foveolar effects of dexamethasone intravitreal implant in central retinal vein occlusion].

AIM: To evaluate functional and morphometric parameters of the central retina in patients with postocclusive macular edema treated with dexamethasone intravitreal implant injection. MATERIAL AND METHODS: We examined 5 patients (5 eyes) with newly diagnosed central retinal vein occlusion complicated by macular edema, including 4 men and 1 woman aged 55.8±3.65 years (experimental group). All the patients received a single injection of dexamethasone intravitreal implant. The maximum follow-up period was 12 months. The control group consisted of 5 presbiopic patients (10 eyes) aged 59.14±3.14 years. RESULTS: One month after injection, the best corrected visual acuity (BCVA) and central retinal light sensitivity improved (from 0.09±0.03 to 0.19±0.05 and from 3.18±0.19 to 11.07±0.97 dB, correspondingly), while foveolar thickness decreased from 425.36±57.87 to 273.75±36.65 µm. One year after the treatment, BCVA remained high and averaged 0.21±0.14. The total light sensitivity also remained higher than that at baseline, however, decreased down to 4.8±0.76 dB. Optical coherence tomography showed some flatness of the fovea. Foveolar thickness appeared 1.5 times higher than that in the control group and 1.2 times higher than that at the 1-month follow-up after dexamethasone intravitreal implant injection. Over the whole follow-up period, IOP has never significantly exceeded the baseline, optical media remained clear. CONCLUSION: 1. Dexamethasone intravitreal implant has been shown effective in resolving postocclusive macular edema, improving visual functions, and increasing central retinal light sensitivity within the first month after injection. 2. Positive changes in morphometric parameters of the central retina induced by the injection involve inner segments of photoreceptors as well as the outer nuclear, outer plexiform and inner nuclear layers. The morphofunctional effect persists for no less than 12 months after injection. 3. Over the 1-year follow-up period, there has been no negative influence of the implant on either intraocular pressure level, or lens transparency.

Perifoveal retinal thickness changes after intravitreal aflibercept injection for choroidal neovascularization in age-related macular degeneration.

OBJECTIVE: There has been some concern that anti-vascular growth factor treatment accelerates the development of macular atrophy in eyes with neovascular age-related macular degeneration. During the treatment with aflibercept, the thickness of choroid may decrease. This may lead to photoreceptor death. The rod cells are more susceptible to atrophic changes than cones during the disease. We aimed to find any thickness changes in the perifoveal outer nuclear layer, where the highest density of rods is found, during the aflibercept intravitreal injection therapy. MATERIALS AND METHODS: Retrospectively, forty-two patients who were treated for age-related macular degeneration with choroidal neovascularization were included in the study. After the first three loading doses, intravitreal injections were repeated every two months. Outer nuclear layer thicknesses were measured 2000 µm away from the center of the fovea with OCT, at a total of 20 points, located at 180 and 90°. The mean of these measurements was obtained before the treatment and 1 year after the therapy. Results were compared by using the Wilcoxon Rank Test. RESULTS: The mean visual acuity was 1,11±0,287 logMAR at the beginning and increased to 0,53±0,32 LogMAR after. Perifoveal thickness was significantly reduced when compared with the thickness before the treatment (p = 0.039, p < 0.05). This result was also significantly lower than the control group thicknesses (p = 0.035, p < 0.05). CONCLUSION: Anti-VEGFs can cause loss of phagocytic functions of RPE. The mechanism of the observed thinning of the ONL may be described as follows: VEGF emitted by the RPE normally helps to maintain the choriocapillaris. Thus, injecting an anti-VEGF intravitreally causes RPE atrophy, which leads to a decrease in the choroidal vascular index. This in turn causes first the rods, and later the cones, that are part of the outer nuclear layer, to start to die and disappear, hence the thinning of this layer. As aflibercept consists of parts of the extracellular domain of both the VEGFR1 and VEGFR2 receptors, that are held together by a human IgG1 backbone, this makes the binding of aflibercept to VEGF-A and VEGF-B stronger as compared to the binding of the previously used ranibizumab or bevacizumab (by nearly a factor 100 in the case of the most abundant isoform VEGF-A 165). Besides, aflibercept also binds very well to placental growth factor (PIGF), which is also associated with several ocular diseases.

Correlation of foveal microstructural changes with vision after anti-vascular endothelial growth factor therapy in age-related macular degeneration.

PURPOSE: To investigate the correlation of foveal microstructural changes with vision after intravitreal ranibizumab injection in eye with choroidal neovascularization (CNV) secondary to age-related macular degeneration. METHODS: We retrospectively studied 40 eyes of 40 patients with neovascular age-related macular degeneration who had no previous treatment history of age-related macular degeneration. All patients were treated with 3 monthly intravitreal ranibizumab (0.5 mg/0.05 mL) injections. One month after the third consecutive injection, best-corrected visual acuity (BCVA) was evaluated and the eyes were categorized into 2 groups according to the change in BCVA (good function group: BCVA improvement ≥ logarithm of minimum angle of resolution 0.3; poor function group: BCVA improvement < logarithm of minimum angle of resolution 0.3). Changes of foveal photoreceptor layer integrity, CNV size (diameter and thickness), central macular thickness, center point thickness, outer nuclear layer thickness, and subretinal fluid in each group were also evaluated using spectral-domain optical coherence tomography. RESULTS: The good function group is 20 eyes, and the poor function group is 20 eyes. No significant differences in baseline characteristics of variables including CNV type, initial BCVA, photoreceptor integrity, and CNV size were observed between the two groups. Best-corrected visual acuity in the good function group was 0.30 ± 0.17 (logarithm of minimum angle of resolution) and that in the poor function group was 0.48 ± 0.40 (logarithm of minimum angle of resolution). Decreased disrupted length of photoreceptor layer (1,020.80 ± 974.60) and decreased CNV thickness (78.86 ± 50.78) were found in the good function group at the end of follow-up. However, no significant differences in changes of CNV diameter, central macular thickness, center point thickness, outer nuclear layer thickness, and resolution of subretinal fluid were observed between the two groups. CONCLUSION: Restoration of foveal photoreceptor integrity and decreased CNV thickness are closely associated with visual improvement in neovascular age-related macular degeneration after treatment.

Intravitreal pegaptanib sodium (Macugen®) for treatment of diabetic macular oedema: a morphologic and functional study.

AIMS: To study whether morphologic (foveal thickness, FT) variations of clinically significant macular oedema (CMO) in patients suffering from diabetes following intravitreal pegaptanib sodium (IVP) injection were associated with functional [macular sensitivity (MS) and colour discrimination (CD)] changes. METHODS: A longitudinal, interventional, non-randomized study was performed. FT was assessed by optical coherence tomography (OCT), MS by microperimetry, best-corrected visual acuity (BCVA) by early treatment diabetic retinopathy study charts (ETDRS) and CD by Farnswoth-Munsell test. The treatment protocol consisted of three consecutive injections (0.3 mg/0.05 ml; baseline, week 6 and week 12). Follow-up checks were scheduled at 18, 24, 36 and 48 weeks, after injections. RESULTS: Thirty eyes of 30 patients with clinically significant CMO were included for analysis. After IVP a significant decrease of FT occurred with a mean reduction from baseline of 56.9% (P= 0.0001). An improvement of functional parameters was recorded in all patients (BCVA from 18.2 ± 8.5 letters to 25.5 ± 8.4 letters, P < 0.005, MS from 8.6 ± 2.16 dB to 10.6 ± 2.61 dB, P < 0.001, colour analysis from 376.1 ± 125.6 TES to 116 ± 34.6 TES, P= 0.0001). A statistically significant correlation between FT and BCVA as well as MS and CD was also found. Neither ocular nor systemic adverse events were reported. CONCLUSIONS: Intravitreal pegaptanib significantly reduced FT, with a concomitant improvement of MS and CD. This association emphasizes the efficacy of IVP in the treatment of CMO.

The 1-year results of CLEAR-IT 2, a phase 2 study of vascular endothelial growth factor trap-eye dosed as-needed after 12-week fixed dosing.

OBJECTIVE: To evaluate anatomic outcomes and vision, injection frequency, and safety during the as-needed (PRN) treatment phase of a study evaluating a 12-week fixed dosing period followed by PRN dosing to week 52 with vascular endothelial growth factor (VEGF) Trap-Eye for neovascular (wet) age-related macular degeneration (AMD). DESIGN: Multicenter, randomized, double-masked trial. PARTICIPANTS: We included 159 patients with subfoveal choroidal neovascularization (CNV) secondary to wet AMD. METHODS: Patients were randomly assigned to 1 of 5 intravitreal VEGF Trap-Eye treatment groups: 0.5 mg or 2 mg every 4 weeks or 0.5, 2, or 4 mg every 12 weeks during the fixed-dosing period (weeks 1-12). From weeks 16 to 52, patients were evaluated monthly and were retreated PRN with their assigned dose (0.5, 2, or 4 mg). MAIN OUTCOME MEASURES: Change in central retinal/lesion thickness (CR/LT), change in total lesion and CNV size, mean change in best-corrected visual acuity (BCVA), proportion of patients with 15-letter loss or gain, time to first PRN injection, reinjection frequency, and safety at week 52. RESULTS: The decrease in CR/LT at week 12 versus baseline remained significant at weeks 12 to 52 (-130 µm from baseline at week 52) and CNV size regressed from baseline by 2.21 mm(2) at 48 weeks. After achieving a significant improvement in BCVA during the 12-week, fixed-dosing phase for all groups combined, PRN dosing for 40 weeks maintained improvements in BCVA to 52 weeks (5.3-letter gain; P<0.0001). The most robust improvements and consistent maintenance of visual acuity generally occurred in patients initially dosed with 2 mg every 4 weeks for 12 weeks, demonstrating a gain of 9 letters at 52 weeks. Overall, a mean of 2 injections was administered after the 12-week fixed-dosing phase, and the mean time to first reinjection was 129 days; 19% of patients received no injections and 45% received 1 or 2 injections. Treatment with VEGF Trap-Eye was generally safe and well tolerated, with few ocular or systemic adverse events. CONCLUSIONS: PRN dosing with VEGF Trap-Eye at weeks 16-52 maintained the significant anatomic and vision improvements established during the 12-week fixed-dosing phase with a low frequency of reinjections. Repeated dosing with VEGF Trap-Eye was well tolerated over 52 weeks of treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Primary endpoint results of a phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration.

OBJECTIVE: To evaluate the biologic effects and safety of vascular endothelial growth factor (VEGF) Trap-Eye during a 12-week fixed-dosing period in patients with neovascular (wet) age-related macular degeneration (AMD). DESIGN: Multicenter, prospective, randomized, double-masked clinical trial with initial 12-week fixed dosing period. Data were analyzed to week 16. PARTICIPANTS: We included 159 patients with subfoveal choroidal neovascularization secondary to wet AMD. METHODS: Patients were randomized 1:1:1:1:1 to VEGF Trap-Eye during the fixed-dosing phase (day 1 to week 12): 0.5 or 2 mg every 4 weeks (0.5 mg q4wk, 2 mg q4wk) on day 1 and at weeks 4, 8, and 12; or 0.5, 2, or 4 mg every 12 weeks (0.5 mg q12wk, 2 mg q12wk, or 4 mg q12wk) on day 1 and at week 12. MAIN OUTCOME MEASURES: The primary endpoint was change from baseline in central retinal/lesion thickness (CR/LT) at week 12; secondary outcomes included change in best-corrected visual acuity (BCVA), proportion of patients with a gain of ≥ 15 letters, proportion of patients with a loss of >15 letters, and safety. RESULTS: At week 12, treatment with VEGF Trap-Eye resulted in a significant mean decrease in CR/LT of 119 µm from baseline in all groups combined (P<0.0001). The reduction in CR/LT with the 2 mg q4wk and 0.5mg q4wk regimens was significantly greater than each of the quarterly dosing regimens. The BCVA increased significantly by a mean of 5.7 letters at 12 weeks in the combined group (P<0.0001), with the greatest mean gain of >8 letters in the monthly dosing groups. At 8 weeks, BCVA improvements were similar with 2 mg q4wk and 2 mg q12wk dosing. After the last required dose at week 12, CR/LT and visual acuity were maintained or further improved at week 16 in all treatment groups. Ocular adverse events were mild and consistent with safety profiles reported for other intraocular anti-VEGF treatments. CONCLUSIONS: Repeated monthly intravitreal dosing of VEGF Trap-Eye over 12 weeks demonstrated significant reductions in retinal thickness and improvements in visual acuity, and was well-tolerated in patients with neovascular AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Comparison of efficacy and safety between half-fluence and full-fluence photodynamic therapy for chronic central serous chorioretinopathy.

PURPOSE: To compare the efficacy and safety of half-fluence photodynamic therapy (PDT) and conventional PDT in chronic central serous chorioretinopathy. METHODS: A multicenter retrospective comparison study. Retrospective review of 60 patients including 29 patients (34 eyes) who received half-fluence PDT and 31 patients (33 eyes) who received conventional PDT for the treatment of chronic central serous chorioretinopathy. Best-corrected visual acuity, central fovea retinal thickness and resolution of subretinal fluid on optical coherence tomography, and choroidal perfusion decrease on indocyanine green angiography were assessed. Choriocapillaris perfusion decrease was quantified as mean gray value ratio of treated and nontreated areas using commercial imaging software. RESULTS: Treatment success without recurrence was achieved in 32 of 34 eyes (94.1%) treated with half-fluence PDT and 33 of 33 eyes (100%) treated with conventional PDT (P = 0.493). There was no difference in final best-corrected visual acuity (logarithm of the minimal angle of resolution) between the 2 groups (0.17 ± 0.32 vs. 0.21 ± 0.39; P = 0.603). Choriocapillaris perfusion decrease quantified from post-PDT indocyanine green angiography was significantly more severe in the conventional PDT group (P = 0.006), and it showed a positive correlation with retinal thinning after PDT (R = 0.380; P < 0.001). CONCLUSION: Half-fluence PDT is as effective as conventional PDT, while minimizing the deleterious effect on choriocapillaris perfusion and retinal thickness.

Efficacy and safety of intravitreal bevacizumab compared with intravitreal and posterior sub-tenon triamcinolone acetonide for treatment of uveitic cystoid macular edema.

PURPOSE: To demonstrate the effect of bevacizumab compared with triamcinolone acetonide for the treatment of persistent cystoid macular edema in noninfectious uveitis. METHODS: The medical records of 31 eyes of 31 patients with uveitic cystoid macular edema that had persisted despite conventional treatment were reviewed. Ten eyes received 1.25 mg of intravitreal bevacizumab (IVB), 11 eyes received 4 mg of intravitreal triamcinolone acetonide (IVTA), and 10 eyes received 40 mg of posterior sub-Tenon triamcinolone acetonide (PSTA). Changes in visual acuity with a logarithmic minimal angle of resolution and central foveal thickness measured with optical coherence tomography were analyzed. RESULTS: The mean follow-up was 22.3 weeks. The best improvement in visual acuity and reduction in central foveal thickness was achieved at 4 weeks in all groups but worsened with time until 12 weeks (visual acuity improved from baseline by 0.19, 0.27, and 0.16 and central foveal thickness decreased from baseline by 167.4 mm, 327.6 mm, and 166.4 mm with IVB,IVTA, and PSTA, respectively; P , 0.001). The results with IVTA were better than those with IVB or PSTA, although the difference did not reach statistical significance. Intravitreal bevacizumab provided a significantly better effect in visual acuity gain in Behcet uveitis than in non-Behcet uveitis (P = 0.045). Kaplan­Meier survival analysis showed that the median period of effect were 16 weeks with IVB, 30 weeks with IVTA, and 12 weeks with PSTA.An increase in intraocular pressure (.5 mmHg greater than baseline) was observed in 1 eye(10%) with IVB, 5 eyes (45.5%) with IVTA, and 4 eyes (40%) with PSTA. CONCLUSION: Intravitreal bevacizumab was a well-tolerated and effective supplementary therapy for persistent uveitic cystoid macular edema, especially in Behcet uveitis and for patients with the risk of an increase in intraocular pressure. However, reinjection may be required because of the limited potency and duration of the positive effects of IVB.

Viscoat versus Visthesia during phacoemulsification cataract surgery: corneal and foveal changes.

BACKGROUND: Ophthalmic viscosurgical devices (OVDs) are widely used in phacoemulsification cataract surgery to maintain adequate intraocular space, stabilize ocular tissue during the operation and decrease the possible damage of the corneal endothelium. Our study has the purpose to compare the corneal and foveal changes of Viscoat and Visthesia in patients undergoing uneventful phacoemulsification cataract surgery. METHODS: Participants in our study were 77 consecutive patients, who were randomized into two groups based on type of OVD used during phacoemulsification: Viscoat or Visthesia. All patients underwent a complete ophthalmological examination i.e., measurement of best corrected visual acuity (BCVA) by means of Snellen charts, intraocular pressure examination by Goldmann tonometry, slit lamp examination, fundus examination, optical coherence tomography, specular microscopy and ultrasound pachymetry preoperatively and at three time points postoperatively (day 3, 15, 28 postoperatively). The differences in baseline characteristics, as well as in outcomes between the two groups were compared by Mann-Whitney-Wilcoxon test and Student's t-test, as appropriate. RESULTS: Intraoperatively, there was no statistically significant difference in the duration of the ultrasound application between the two groups, while Viscoat group needed more time for the operation performance. It is also worthy to mention that Visthesia group exhibited less intense pain than patients in Viscoat group. Postoperatively, there was a statistically significant difference in central corneal thickness, endothelial cell count and macular thickness between the two groups, but BCVA (logMAR) did not differ between the two groups. CONCLUSIONS: Our study suggests that Viscoat is more safe and protective for the corneal endothelium during uneventful phacoemulsification cataract surgery, while Visthesia is in superior position regarding intraoperative pain. Patients of both groups acquired excellent visual acuity postoperative. Finally, this is the first study comparing OVDs in terms of macular thickness, finding that Visthesia cause a greater increase in macular thickness postoperatively than Viscoat, although it reaches normal ranges in both groups.

Early Postnatal Oxygen Exposure Predicts Choroidal Thinning in Neonates.

Purpose: To evaluate whether choroidal thickness (CT) using arm-mounted optical coherence tomography (OCT) in infants screened for retinopathy of prematurity (ROP) correlates with oxygen exposure in neonates. Methods: OCT images were obtained in infants screened for ROP in a single level IV neonatal intensive care unit. CT was measured at three different locations: the subfoveal center and 1.5 mm from the fovea center in each direction. Correlation and regression analyses were performed to determine the relationship between clinical factors and CT. Clinical factors included gestational age, birth weight, presence of bronchopulmonary dysplasia (BPD), and fraction of inspired oxygen (FiO2) at defined time points: 30 weeks postmenstrual age (PMA), 36 weeks PMA, and on day of imaging. Results: Mean subfoveal, nasal, and temporal choroidal thicknesses CT (SFCT, NCT, and TCT, respectively) were 228.0 ± 51.4 µm, 179.7 ± 50.3 µm, and 186.4 ± 43.8 µm, respectively. SFCT was found to be significantly thicker than NCT and TCT (P < 0.0001 and P = 0.0002, respectively), but no significant difference was found between NCT and TCT (P = 0.547). Compared with infants without BPD, infants with BPD had thinner SFCT and NCT (P = 0.01 and P = 0.0008, respectively). Birth weight was positively correlated with SFCT (r = 0.39, P = 0.01) and NCT (r = 0.33, P = 0.045) but not TCT. Gestational age and ROP stage were not significantly associated with CT. SFCT was found to be significantly thinner with higher average FiO2 supplementation levels at 30 weeks PMA (r = -0.51, P = 0.01) but not at 36 weeks PMA. Regression analysis revealed that FiO2 at 30 weeks PMA was an independent predictor of SFCT in infants screened for ROP (P = 0.01). Conclusions: Early postnatal exposure (<32 weeks PMA) to higher oxygen supplementation in premature neonates statistically predicts choroidal thinning.

Resolution of bilateral foveal cysts in dome-shaped macula after treatment with topical dorzolamide.

Dome-shaped macula (DSM) is characterised by a convex anterior bulging of the macular area. It can further get complicated by accumulation of subretinal fluid (SRF). Foveal cysts that are bilateral, in a setting of DSM, are an entity not yet reported. Management options for DSM with SRF showed variable success. Topical carbonic anhydrase inhibitors (CAIs) have been successful in treating certain macular pathologies. The authors report a rare case of bilateral intraretinal foveal cyst in a myopic child with DSM with favourable response to topical dorzolamide. Topical CAIs may be considered a safe and effective option in such cases.