Comparison of Retinal Layer Thickness in Eyes with Resolved Diabetic Macular Edema Receiving Ranibizumab with Normal Eyes.

PURPOSE: To evaluate the thickness of individual retinal layers in eyes with resolved diabetic macular edema (DME) after treatment with ranibizumab (RBZ). METHODS: Spectral-domain optical coherence tomography (OCT) scans of 25 eyes (25 patients) with DME that had been treated with RBZ (and shown resolution of edema as evident by the absence of fluid in a high-resolution grid placed on the fovea) were acquired using Spectralis HRA + OCTTM. Thickness measurements of individual layers were calculated using papillomacular bundle (PMB), central subfield, and inner- and outer-ring Early Treatment Diabetic Retinopathy Study (ETDRS) grids. Measurements were compared to 45 normal eyes with no known retinal disease. A post-hoc analysis was done correlating visual acuity (VA) with individual retinal layer thickness. RESULTS: Full retinal thickness (FRT) was thinner than normal individuals across all 4 grids. There were similarities and differences among the 4 grids; however, PMB and inner-ring ETDRS grids displayed the most resemblance. The VA significantly correlated with the FRT measured in PMB (p = 0.004), central subfield (p = 0.02), and inner-ring (p = 0.006) ETDRS. CONCLUSIONS: Segmentation of OCT scans revealed significant differences in the overall thickness of the retina and of individual retinal layers in patients with resolved DME. PMB grid showed a stronger correlation between affected retinal layers and VA compared to ETDRS. PMB also showed significance with VA in layers that were shown to be not significant in ETDRS grid.

Analysis of orbital malignancies presenting in a tertiary care hospital in Pakistan.

OBJECTIVE: To determine the frequencies of various orbital malignancies amongst orbital lesions in patients presenting in a tertiary care hospital in Pakistan. METHODS: A retrospective analysis of 666 orbital cases with an established histopathological diagnosis of malignant tumors treated in Mayo Hospital Lahore from 1996 to 2015 (20 years). RESULTS: About 66% of the malignant tumors were primary, 25% secondary, 8% haematopoietic and 1% metastatic. Almost 50% of the cases were children. Retinoblastoma is the commonest tumor (43% overall and 87% among children). Squamous cell carcinoma is the second commonest (15.6% overall and 31% among adults). These are then followed by Adenoid cystic carcinoma of Lacrimal Gland (9%), Lymphoma/Leukaemia (8%) and Rhabdomyosarcoma (6.3%). CONCLUSION: Frequencies of various orbital malignancies show geographical variation in both paediatric and adult population.

Effect of Vitreomacular Adhesion on Treatment Outcomes in the Ranibizumab for Edema of the Macula in Diabetes (READ-3) Study.

PURPOSE: To assess the role of vitreomacular adhesion (VMA) in visual and anatomic outcomes in patients with diabetic macular edema (DME). DESIGN: Retrospective cohort study. PARTICIPANTS: Data from patients enrolled in the Ranibizumab for Edema of the Macula in Diabetes: Protocol 3 with High Dose (READ-3) study were analyzed. METHODS: In the READ-3 study, patients with DME received monthly intravitreal injections of either 0.5 or 2.0 mg ranibizumab. Optical coherence tomography images from patients who completed the month 6 visit of the study were analyzed at the baseline visit to identify the presence (VMA+) or absence (VMA-) of VMA. Patients with any degree of vitreomacular traction were excluded from the analysis. Two independent graders graded all images. Vitreomacular adhesion was classified by size of adhesion into either focal (<1500 µm) or broad (≥1500 µm). MAIN OUTCOME MEASURES: Mean changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) at month 6 and incidence of posterior vitreous detachment (PVD). RESULTS: One hundred fifty-two eyes (152 patients) were randomized in the READ-3 study. One hundred twenty-four eyes (124 patients) were eligible for the study based on study criteria. Twenty-eight eyes did not meet study criteria and were excluded from the study. At baseline, 26 patients were classified as VMA+ and 98 patients were classified as VMA-. The distribution of the 2 doses of ranibizumab (0.5 and 2.0 mg) in the 2 groups was similar. At month 6, the mean improvement in BCVA was 11.31±6.67 and 6.86±7.58 letters in the VMA+ and VMA- groups, respectively (P = 0.007). Mean improvement in CRT was -173.81±132.31 and -161.84±131.34 µm in the VMA+ and VMA- groups, respectively (P = 0.681). At month 6, among the 26 VMA+ eyes (at baseline), 7 eyes demonstrated PVD, 17 eyes showed no change in VMA status, and 2 eyes were not gradable and were excluded. CONCLUSIONS: Diabetic macular edema patients with VMA have a greater potential for improvement in visual outcomes with anti-vascular endothelial growth factor therapy. Therefore, the presence of VMA should not preclude patients with DME from receiving treatment.

Twenty-four-Month Outcomes of the Ranibizumab for Edema of the Macula in Diabetes - Protocol 3 with High Dose (READ-3) Study.

PURPOSE: To compare 2.0 mg ranibizumab (RBZ) injections with 0.5 mg RBZ for eyes with center-involved diabetic macular edema (DME). DESIGN: Randomized, controlled, double-masked (to the dose), interventional, multicenter clinical trial. PARTICIPANTS: A total of 152 patients (152 eyes) with DME. METHODS: Eligible eyes were randomized in a 1:1 ratio to 0.5 mg (n = 77) or 2.0 mg (n = 75) RBZ. Study eyes received 6 monthly mandatory injections followed by as-needed injections until month 24. MAIN OUTCOME MEASURES: The primary efficacy end point of the study was mean change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at month 6. Secondary outcomes included the mean change in BCVA and CFT at month 24, and incidence and severity of systemic and ocular adverse events through month 24. RESULTS: A total of 152 eyes were randomized in the study. At month 24, the mean improvement from baseline BCVA was +11.06 letters in the 0.5 mg RBZ group (n = 59) and +6.78 letters in the 2.0 mg RBZ group (n = 54) (P = 0.02). The mean numbers of RBZ injections through month 24 were 18.4 and 17.3 in the 0.5 mg and 2.0 mg RBZ groups, respectively (P = 0.08). The mean change in CFT was -192.53 µm in the 0.5 mg RBZ group and -170.64 µm in the 2.0 mg RBZ group (P = 0.41). By month 24, 3 deaths had occurred in the 0.5 mg RBZ group and 3 deaths had occurred in the 2.0 mg RBZ group; 5 of these 6 deaths occurred secondary to cardiovascular causes, and 1 death occurred as the result of severe pneumonia. All 5 patients with a cardiovascular cause of death had a history of coronary heart disease. CONCLUSIONS: At month 24, there were significant visual and anatomic improvements in both groups, with subjects in the 0.5 mg RBZ group gaining more vision. Visual and anatomic gains achieved at month 6 were largely maintained through month 24. No new safety events were identified. In this study population, 2.0 mg RBZ does not appear to provide additional benefit over 0.5 mg RBZ.

Aflibercept for neovascular age-related macular degeneration.

BACKGROUND: Central vision loss caused by age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Neovascular AMD is characterized by choroidal neovascularization (CNV). Growth of new blood vessels in patients with neovascular AMD is driven by a complex process that involves a signal protein called vascular endothelial growth factor A (VEGF-A). Anti-VEGF drugs that block this protein include ranibizumab, bevacizumab, and aflibercept. OBJECTIVES: To assess and compare the effectiveness and safety of intravitreal injections of aflibercept versus ranibizumab, bevacizumab, or sham for treatment of patients with neovascular AMD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (Issue 11, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched December 4, 2014), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on November 30, 2015. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which aflibercept monotherapy was compared with ranibizumab, bevacizumab, or sham for participants with neovascular AMD who were treatment-naive. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures of The Cochrane Collaboration for screening, data abstraction, and study assessment. Two review authors independently screened records, abstracted data, and assessed risk of bias of included studies; we resolved discrepancies by discussion or with the help of a third review author when needed. MAIN RESULTS: We included two RCTs (total of 2457 participants, 2457 eyes). Trial participants had neovascular AMD with active subfoveal choroidal neovascular lesions. Both trials followed the same protocol and compared aflibercept at various doses versus ranibizumab, but they were carried out in different countries. One trial enrolled participants from the United States and Canada, and the second trial was conducted at 172 sites in Europe, Asia Pacific, Latin America, and the Middle East. The overall quality of the evidence was high, and included trials were at low risk for most bias domains assessed; however, both trials were funded by the manufacturers of aflibercept. For the purposes of analysis, we combined aflibercept groups regardless of dosing and analyzed them as a single group.Visual acuity outcomes were similar between aflibercept and ranibizumab groups; at one year, participants in the aflibercept groups showed mean change in best-corrected visual acuity (BCVA) from baseline similar to that of participants in the ranibizumab groups (mean difference (MD) -0.15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, 95% confidence interval (95% CI) -1.47 to 1.17; high-quality evidence). At two years, the mean change in BCVA from baseline was 7.2 ETDRS letters for aflibercept groups versus 7.9 for ranibizumab groups. Sufficient data were not available for calculation of confidence intervals.The proportion of participants who gained 15 or more letters of BCVA by one year of follow-up was approximately 32% for both aflibercept and ranibizumab (RR 0.97, 95% CI 0.85 to 1.11; high-quality evidence), and by two years of follow-up was approximately 31% (RR 0.98, 95% CI 0.85 to 1.12; high-quality evidence). Similar small proportions of participants in the aflibercept and ranibizumab groups lost 15 or more letters of BCVA at one year (RR 0.89, 95% CI 0.61 to 1.30; high-quality evidence); this outcome was not reported for two-year follow-up. Data were not reported on the proportion of participants with BCVA worse than 20/200 at one- or two-year follow-up.Participants treated with aflibercept or ranibizumab showed similar improvement in morphological outcomes, as assessed from images (central retinal thickness and CNV size). At one year, the proportion of eyes that achieved dry retina was similar between aflibercept and ranibizumab groups (absence of cystic intraretinal fluid and subretinal fluid on optical coherence tomography (OCT); RR 1.06, 95% CI 0.98 to 1.14; high-quality evidence). In addition, investigators reported no difference in reduction of CNV area between aflibercept- and ranibizumab-treated eyes at one year (MD -0.24 mm(2), 95% CI -0.78 to 0.29; high-quality evidence). Data were not reported for the proportion of eyes with absence of leakage on fluorescein angiography at one- or two-year follow-up.Overall, occurrence of serious systemic adverse events was similar and comparable in aflibercept- and ranibizumab-treated groups at one year (RR 0.99, 95% CI 0.79 to 1.25). Risk of any serious ocular adverse event was lower in the aflibercept group than in the ranibizumab group, but the risk estimate is imprecise (RR 0.62, 95% CI 0.36 to 1.07). As the result of imprecision, we graded the quality of evidence for all adverse events as moderate. AUTHORS' CONCLUSIONS: Results of this review document the comparative effectiveness of aflibercept versus ranibizumab for visual acuity and morphological outcomes in eyes with neovascular AMD. Current available information on adverse effects of each medication suggests that the safety profile of aflibercept is comparable with that of ranibizumab; however, the number of participants who experienced adverse events was small, leading to imprecise estimates of absolute and relative effect sizes. The eight-week dosing regimen of aflibercept represents reduced treatment requirements in comparison with monthly dosing regimens and thus has the potential to reduce treatment burden and risks associated with frequent injections.

Novel Therapies in Development for Diabetic Macular Edema.

Diabetic macular edema (DME) secondary to diabetic retinopathy (DR) is a major cause for functional visual loss in the developed world. Laser photocoagulation has been used for decades in the treatment of DME. However, the advent of anti-vascular endothelial growth factor (anti-VEGF) has revolutionized the treatment of DME. Three important anti-VEGF agents whose efficacy has been well established via phase III clinical trials include ranibizumab, bevacizumab, and aflibercept. However, even in the era of anti-VEGF therapies, there are some challenges that retina specialists have to confront in managing patients with DME. These include the need for frequent treatment and an unpredictable response to therapy. There is evidence to suggest that pathways other than the VEGF pathway may be playing a role in the development of DME. Thus, extensive research is focused on development of novel agents that target these pathways. This review focuses on novel therapeutic agents in development, which may be used as a monotherapy or in combination with anti-VEGF agents, for the management of DME in the future.

Screw implantation in the globe: the risk of delayed hardware migration from craniofacial repair.

Plating system modification has enabled the use of rigid fixation in younger patients having maxillofacial surgery. One of the common reported complications of the use of plates and screws in children is screw migration due to skeletal maturation. Ophthalmic complications due to maxillofacial surgery reported to date include oculomotor and abducens palsies, lacrimal damage and vision loss due to infection, retrobulbar hemorrhage, and compartment syndrome. We describe a complication unique to screw migration resulting in orbital fixation and near-globe rupture in a patient with Treacher Collins syndrome. We hope to alert our colleagues to the potential risk of screw and hardware migration and breakage, particularly in the setting of craniofacial surgery performed on a child before maturation of craniofacial osseous structures.

A case of orbital apex syndrome in a patient with malignant otitis externa.

A rare case of skull base infection with a rapid clinical course leading to visual loss and eventually death in a poorly-controlled diabetic patient is presented. A 37-year-old woman presented with a history of visual loss and painful protrusion of the right eye for the preceding 3 days.This was accompanied by vertigo and right-side facial weakness. The patient had perception of light in her right eye and 20/25 (presenting visual acuity) in the fellow eye, accompanied by right-side proptosis, total ophthalmoplegia, optic disc pallor and central retinal artery occlusion. Magnetic resonance imaging showed the presence of oedema with soft-tissue thickening in the right external auditory canal along with evidence of fluid within the middle ear cavity and mastoid air cells on the right side. A diagnosis of Orbital Apex Syndrome was made and treatment initiated.

Utilisation of composite endpoint outcome to assess efficacy of tocilizumab for non-infectious uveitis in the STOP-Uveitis Study.

BACKGROUND/AIMS: To use a composite endpoint scoring system in assessing efficacy of two doses of intravenous tocilizumab (TCZ), in eyes with non-infectious uveitis. METHODS: Data from STOP-Uveitis Study (a phase 2 multicentre, randomised, interventional clinical trial), where monthly intravenous infusions of 4 mg/kg (Group 1) or 8 mg/kg (Group 2) TCZ until month 6 (M6) were administered, were used. Efficacy was ascertained by a composite endpoint scoring system consisting of: (1) visual acuity; (2) intraocular inflammation; (3) central retinal thickness; (4) posterior segment inflammation on fluorescein angiographic and (5) steroid taper. Each component of grading system was graded as ((+1) improvement, (-1) worsening or (0) no change) based on specific criteria. The clinical response was classified as positive (improvement in at least one parameter and worsening in none), negative (worsening of any parameter) or stable (neither improvement nor worsening of any parameter). The percentage achieving various clinical responses was compared between groups. RESULTS: Thirty-seven patients were analysed. At M6, 31 (83.8%) subjects demonstrated a positive clinical response (Group 1=14 (77.8%) and Group 2=17 (89.5%)). Three (8.1%) subjects (all Group 1) met the criteria for treatment failure, whereas three (8.1%) subjects showed a stable clinical response (Group 1=1 and Group 2=2). The difference in clinical responses between study groups was not significant (p>0.05). CONCLUSIONS: Both doses of intravenous TCZ were effective in either improving or maintaining stability in patients using the composite endpoint scoring system. A composite scoring system as used in this study may be a better measure to assess efficacy outcomes as compared with only vitreous haze or other single outcome measures.

Worldwide outcomes of nasal transposition of the split lateral rectus muscle for strabismus associated with 3rd-nerve palsy.

BACKGROUND/AIMS: To determine success rate and complications associated with nasal transposition of the split lateral rectus muscle (NTSLR) for treating strabismus from 3rd-nerve palsy. METHODS: An international, multicentre, registry of patients with unilateral 3rd-nerve palsy treated with NTSLR was created. Patients with concurrent surgery on the contralateral eye were excluded. Primary outcome was horizontal alignment within 15 prism dioptres (PD) of orthotropia. Incidence of technical difficulties and vision-threatening complications by 6 months post-procedure were reported. RESULTS: Ninety-eight patients met inclusion criteria. Median age was 33.5 years (IQR 10.75-46). Aetiologies included congenital (31%), neoplastic (16%) and traumatic (15%). Twenty-five per cent of patients had prior ipsilateral strabismus surgery. Median exotropia decreased from 70PD preoperatively (IQR 50-90) to 1PD postoperatively (IQR 0-15.5), with a success rate of 69%. Performing concurrent superior oblique muscle tenotomy (SOT) was independently associated with success (p=0.001). Technical challenges occurred in 30% of cases, independently associated with a history of ipsilateral strabismus surgery (p=0.01). Eleven per cent of patients had vision-threatening complications, independently associated with more posterior placement of the split lateral rectus (LR) muscle (p<0.001), and most commonly transient serous choroidal effusion. Surgical placement of the split LR muscle within 4.25 mm of the medial rectus (MR) muscle insertion reduced this risk. CONCLUSION: NTSLR significantly improved primary position alignment altered by 3rd-nerve palsy. Concurrent SOT and placement of the split LR muscle ≤4.25 mm posterior to the MR muscle insertion optimised outcomes. NTSLR proved technically challenging when prior ipsilateral strabismus surgery had been performed.

Extraocular muscle ductions following nasal transposition of the split lateral rectus muscle.

OBJECTIVE: To quantify changes in ductions following nasal transposition of the split lateral rectus muscle (NTSLR) for treating third nerve palsy. DESIGN: Retrospective cohort study. PARTICIPANTS: A single eye from each patient with third nerve palsy treated with NTSLR with ocular motility measurements. METHODS: Observation of changes in pre- and postoperative ductions. Outcome measures including patient demographic and surgical factors associated with the ability to adduct beyond the midline after NTSLR were evaluated using multivariable logistic regression. RESULTS: A total of 116 patients met the inclusion criteria for this study. The NTSLR significantly decreased abduction (median of 0 limitation [interquartile range (IQR), 0-0] prior to surgery to -4 [IQR, -4 to -3] after NTSLR; p < 0.001), with a corresponding improvement in adduction (median, -5 [IQR, -5 to -4] prior to surgery to -4 [IQR, -4 to -3] after NTSLR; p < 0.001). There was no change in median supraduction or infraduction after NTSLR (p > 0.05). The ability to adduct beyond the midline after NTSLR was demonstrated in 42% of patients. Although not statistically significant, a trend toward a postoperative ability to adduct beyond the midline was seen in patients who had concurrent superior oblique muscle tenotomy (odds ratio [OR] = 5.08; 95% CI, 0.91-40.9) or who were designated with partial rather than complete third nerve palsy (OR = 2.29; 95% CI, 0.82-6.70). CONCLUSIONS: NTSLR improves the horizontal midline positioning of eyes with third nerve palsy. Most eyes lose the ability to abduct, but some regain a modest ability to adduct while vertical ductions remain unchanged.

Aberrant regeneration in an international registry of patients with 3rd-nerve palsy.

BACKGROUND/AIMS: To describe the patterns of pre-operative aberrant regeneration and motility outcomes reported in an international registry of patients with 3rd-nerve palsy treated with nasal transposition of the split lateral rectus muscle (NTSLR). METHODS: This cross-sectional study used data from an international, multicentre registry of patients with 3rd-nerve palsy treated with NTSLR. Patients with aberrant regeneration were identified, and patterns of innervation described. Demographics and postoperative success defined as horizontal alignment ≤15 PD were compared based on the presence, and type, of aberrant regeneration using Wilcoxon rank sum and Fisher's exact tests. RESULTS: Aberrant regeneration was reported in 16% (21/129) of patients. Age at diagnosis, sex, and aetiology of palsy were not significantly associated with aberrant regeneration. Abnormal movements were triggered by adduction in 52% (11/21), infraduction in 23% (5/21), and supraduction in 23% (5/21) of cases. Presentation patterns involved rectus muscle innervation in 29% (6/21) and levator muscle innervation in 71% (15/21) of cases. Although patients with aberrant regeneration had similar probability of success in comparison to those without following NTLSR (76% vs. 69%, p = 0.5), those with abnormal innervation of a rectus muscle had a lower success rate than those with abnormal innervation of the levator palpebrae superioris muscle (17% vs. 93%; p = 0.002). CONCLUSION: Successful treatment of a 3rd nerve palsy with NTSLR was not influenced by aberrant regeneration involving the levator muscle. Alternative surgical interventions should be considered when aberrant regeneration alters rectus muscle function given its adverse impact on motor outcomes with NTSLR.

Posterior segment inflammatory outcomes assessed using fluorescein angiography in the STOP-UVEITIS study.

BACKGROUND: Although fluorescein angiography (FA) is a frequently used imaging modality in patients with non-infectious uveitis (NIU), it has not been reliably used for objective assessment of posterior segment inflammatory outcomes in these patients. In this index study we report the posterior segment inflammatory outcomes of two different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with NIU using a semi-quantitative FA scoring system. METHODS: STOP-Uveitis is a randomized, multi-center clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with NIU. Thirty-seven (37) patients with NIU were randomized into one of two treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Posterior segment inflammatory outcomes were assessed by evaluating FA at baseline and month 6 by graders at a central reading center. A previously reported, semi-quantitative, scoring system for FA was used to assess signs that represent ongoing inflammatory processes in the posterior segment. These signs included optic disc hyperfluorescence, macular edema, retinal vascular staining and/or leakage, capillary leakage, retinal capillary nonperfusion, neovascularization of the optic disc, neovascularization elsewhere, pinpoint leaks, and retinal staining and/or subretinal pooling. Statistical significance was set at p < 0.05. Main outcome measures included change in posterior segment inflammation as assessed using FA at month 6. RESULTS: 37 eyes (37 patients) were randomized in the STOP-Uveitis study. 30 eyes were found to be eligible for this sub-study based on study criteria. Seven eyes had ungradable images at either baseline or month 6 and were therefore excluded from the analysis. The reduction in FA inflammatory scores at month 6 were statistically significant in both groups (p < 0.05). The difference between the two groups was not significant (p = 0.351). CONCLUSIONS: IV infusions of tocilizumab (both 4 and 8 mg/kg) are effective in improving posterior segment inflammation in eyes with NIU. A semi-quantitative FA scoring system may be used as a reliable outcome measure for assessment of posterior segment inflammation.ClinicalTrials.gov Identifier: NCT01717170.

Pharmacological agents in development for diabetic macular edema.

BACKGROUND: Diabetic macular edema (DME) is the leading cause of visual loss in patients with diabetic retinopathy. There has been a paradigm shift in the treatment of DME since the advent of anti-vascular endothelial growth factor (anti-VEGF) therapy. The safety and efficacy of anti-VEGF therapy has been well established. Although efficacious, currently approved anti-VEGF agents are associated with certain limitations, which include, among others: frequent need for injections, high treatment cost and variable response to treatment. These challenges have led to an active search for more novel agents that may be able to overcome these limitations. AREAS COVERED: The index review focuses on novel treatment agents that target various pathways in patients with DME. These agents are used either as monotherapy or in combination with other agents in the management of DME. Drugs discussed include novel anti-VEGF inhibitors, TIE-2 receptor modulators, integrin peptide inhibitors, rho kinase inhibitors, and future therapies such as neuroprotection and gene therapy. CONCLUSIONS: The future of investigational pharmacological therapy appears promising for patients with DME. Results from early clinical trials indicate that newer agents highlighted in the study may be safe and efficacious treatment options for patients with DME. However, data from large multicenter clinical trials need to be analyzed before these agents can be incorporated into clinical practice.

Correction of perceived visual distortions using a software application and correlation to age-related macular degeneration.

PURPOSE: To investigate the use of software-generated corrections in neutralizing perceived distortions in age-related macular degeneration. METHODS: A tablet-based application was utilized to elicit distortions. Five subjects (seven eyes: neovascular age-related macular degeneration and three eyes: non-neovascular age-related macular degeneration) traced the reference lines, and their distortion traces were recorded. To counter distortion, a software-generated trace was re-traced by subjects to produce a corrected trace. Final traces were superimposed on optical coherence tomography images and following distances calculated: (a) dDT: distance between distortion trace and reference line; (b) dGT: distance between software-generated trace and corrected trace; (c) dCT: distance between corrected trace and reference line. Mean percent improvement in distortion was reported. Mean effectiveness of correction was also reported by utilizing t test to compare dDT and dCT. The number of distortion traces with underlying lesions on optical coherence tomography was also analyzed. RESULTS: Mean age of the subjects was 76.6 (±9.5) years. Each patient traced six reference lines and each was considered a separate case. Out of 30 cases, 17 (56.6%) elicited distortion. Mean percent improvement in distortion was 71.3 ± 23% (p < 0.05). Twelve cases (70.6%) had an underlying lesion (eight cases: disrupted photoreceptor layer and four cases: normal photoreceptor layer). Mean percent improvement in cases with normal photoreceptor layer (90.8 ± 5.45%) was higher than with abnormal photoreceptor layer (58.5 ± 7.17%) (p < 0.05). Five cases with distortion had no associated underlying lesion. Mean percent improvement in these subjects was significantly higher than those with photoreceptor layer disruption. CONCLUSION: Software-generated corrections can potentially correct for perceived distortions in patients with age-related macular degeneration, especially in cases with preserved photoreceptor layer.

Topographic correlation between multifocal electroretinography, microperimetry, and spectral-domain optical coherence tomography of the macula in patients with birdshot chorioretinopathy.

PURPOSE: To correlate the findings of retinal function with multifocal electroretinogram (mfERG), microperimetry (MP), and structural assessments with spectral-domain optical coherence tomography (SD-OCT) in topographically corresponding areas of the macula of patients with birdshot chorioretinopathy (BSCR). METHODS: Patients diagnosed with BSCR by clinical and imaging findings were included in the study. The mfERG was performed using 61 hexagon stimulus patterns grouped into 5 rings (Diagnosys Inc., USA). Individual responses [N1-P1 amplitudes in nanovolt (NV)/degree2 and P1 implicit time in milliseconds (msec)] for each hexagon in the central 3 rings (R1, 0°-2.3°; R2,2.3°-7.7°; and R3, 7.7°-12°) were obtained (19 hexagons). MP examination consisted of Polar 3-12° test with 28 points in 3 concentric rings with diameters of approximately 2.3°, 6.6°, and 11.1° from the foveal center. SD-OCT was performed using macular scans of 20° × 20°. The retinal sensitivity values on MP and thickness values of retinal layers were correlated with the responses on the mfERG for each topographically correlated hexagon. RESULTS: Sixteen eyes of eight patients were included in the study (mean age, 59.87 ± 10.01 years; range, 41-73 years). The amplitudes and the implicit times on mfERG and retinal sensitivities on MP were decreased for each of the 19 hexagons. Considering retinotopically matched points, there was correlation between the retinal sensitivities and mfERG implicit times and response amplitudes in all three rings. The thickness of the retinal pigment epithelium showed modest correlation with the mfERG parameters (ρ = 0.29; p = 0.04). The structural changes on SD-OCT, such as IS-OS disruption, were associated with changes in the mfERG trace arrays. CONCLUSIONS: The structural and functional assessments in retinae of eyes with BSCR suggest that each imaging tool may be capturing unique aspects of retinal dysfunction. Multimodal imaging may allow detailed analyses of retinal damage at various corresponding loci. These findings are important when considering the use of these techniques in BSCR.

Effect of vitreomacular adhesion on the treatment outcomes in the STOP-Uveitis clinical trial for non-infectious uveitis.

PURPOSE: To evaluate the role of vitreomacular adhesion (VMA) in visual and anatomic outcomes in patients with non-infectious uveitis. DESIGN: Phase 2 clinical trial PARTICIPANTS: Data from the Safety, Tolerability, and Efficacy of Tocilizumab in Patients with Non-infectious Uveitis (STOP-Uveitis) study was analyzed. METHODS: In the STOP-Uveitis study, patients with non-infectious uveitis (NIU) received monthly intravenous infusions of either 4 or 8 mg/kg tocilizumab until month 6 (M6). Spectral domain optical coherence tomography (SD-OCT) images of patients that completed M6 of the study were analyzed at baseline to stratify the patients by the presence (VMA+) or absence (VMA-) of VMA. Patients with vitreomacular traction (VMT) or epiretinal membrane causing structural abnormalities within center 1 mm were excluded. All images were graded by two independent graders. MAIN OUTCOME MEASURES: Mean change in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and vitreous haze (VH) at M6. RESULTS: Out of 37 patients randomized in the STOP-Uveitis study, 48 eyes (27 patients) were eligible based on the study criteria. At baseline, 19 eyes were classified as VMA+, and 32 eyes were classified as VMA-. The distribution of two doses of TCZ (4 mg/kg and 8 mg/kg) were similar between the two groups. At M6, the mean improvement in BCVA was 2.00 ± 5.3 and 6.50 ± 7.98 letters in the VMA+ and VMA- groups, respectively (p = 0.02). The mean improvement in CRT was 34.85 ± 72.36 and 80.37 ± 157.21 µm in the VMA+ and VMA- groups, respectively (p = 0.18). Similarly, the mean change in VH was - 0.65 ± 0.47 and - 0.76 ± 0.71 in the VMA+ and VMA- groups, respectively (p = 0.32). Out of 16 eyes with VMA at baseline, 3 eyes developed posterior vitreous detachment (PVD) at M6. The mean change in BCVA was significantly higher (p = 0.02), while CRT and VH score were similar (p > 0.05) in eyes with PVD compared to eyes with persistent VMA. CONCLUSIONS: The absence of VMA or development of PVD in eyes with VMA seems to have a beneficial effect on the vision of subjects receiving treatment for uveitis. Therefore, patients with uveitis should be assessed using SD-OCT for the presence of vitreomacular interface abnormalities.

Diurnal variation of choriocapillaris vessel flow density in normal subjects measured using optical coherence tomography angiography.

BACKGROUND: Vessel flow density (VFD) may provide important information regarding perfusion status. Diurnal variation in VFD of choriocapillaris has not been reported in literature. In the index study, optical coherence tomography angiography (OCTA) was used to assess the diurnal variation of the VFD in the choriocapillaris of subjects with no known ocular disease. METHODS: Fifty eyes with no known ocular disease (25 subjects) were included. OCTA images were acquired using AngioVue (Optovue, Fremont, CA, USA) at two different time points on a single day: 9:00 AM and 6:00 PM. Macular cube scan protocol (3 × 3 mm) centered on the fovea was used. Automatic segmentation of the retinal layers and choriocapillaris was performed using ReVue software, which was also used to measure the choriocapillaris VFD. Horizontal line scan passing through fovea was obtained by the device at both time points to measure the subfoveal choroidal thickness (CT). Linear measurement tool of software was used to measure subfoveal CT according to a standardized reproducible method. Wilcoxon signed-rank test was used to assess the differences in choriocapillaris VFD and subfoveal CT at the two time points. Correlation between change in choriocapillaris VFD and subfoveal CT at the two time points was assessed using the Pearson correlation coefficient (r). RESULTS: The mean age of the subjects was 31.96 ± 11.23 years. Choriocapillaris VFD was significantly higher at 9:00 AM compared to 6:00 PM (P < 0.0001) with mean choriocapillaris VFD of 68.74 ± 4.80% at 9:00 AM and 67.57 ± 5.41% at 6:00 PM, with a mean diurnal amplitude of 1.17%. Mean subfoveal CT was 287.74 ± 61.51 µm at 9:00 AM and 270.06 ± 60.73 µm at 6:00 PM. Subfoveal CT was also significantly higher at 9:00 AM compared to 6:00 PM (P < 0.0001) with a mean diurnal amplitude of 17.68 µm. Change in choriocapillaris VFD correlated with change in subfoveal CT (r = 0.87, P < 0.001). CONCLUSION: OCTA demonstrated significant diurnal change in choriocapillaris VFD in subjects without any ocular disease with VFD being higher in the morning and lower in the evening. Decrease in choriocapillaris VFD in the evening correlated with a reduction in subfoveal CT.