Hamid Hosseini

Intravitreal infliximab for the treatment of sight-threatening chronic noninfectious uveitis.

Purpose: Tumor necrosis factor-alpha is known to play an important role in various immune-mediated ocular diseases. Infliximab, a chimeric monoclonal antibody against tumor necrosis factor-alpha, has been used for the treatment of various chronic systemic and ocular inflammatory diseases. The purpose of this study was to evaluate the effect of intravitreal injection of infliximab on the visual acuity and central macular thickness in patients with chronic noninfectious uveitis. Methods: Ten eyes of 7 patients with chronic persistent noninfectious uveitis who were nonresponsive to conventional previous medications during the previous 3 months were included in this study. The patients received intravitreal injection of 1.5 mg/0.15 mL infliximab. Mean best-corrected visual acuity and mean central macular thickness 1 day before and 4 weeks after the injection were evaluated and compared. Results: Mean logarithm of the minimum angle of resolution before and after injection was 1.37 ± 0.43 and 0.67 ± 0.56, respectively, with statistically significant improvement after injection (P = 0.005). The mean central macular thickness before and after injection was 673.20 ± 338.39 μm and 456.40 ± 317.46 μm, respectively, with a significant decrease in the central macular thickness after the injection (P = 0.005). Conclusion: Intravitreal injection of infliximab may improve the visual acuity and decrease the central macular thickness in patients with chronic noninfectious uveitis and significant visual loss and central macular edema.

Measurement of optic disc size and rim area with spectral-domain OCT and scanning laser ophthalmoscopy.

PURPOSEnTo compare optic disc and neuroretinal rim area measurements from spectral-domain optical coherence tomography (SD-OCT) to those from confocal scanning laser ophthalmoscopy.nnnMETHODSnSeventy-one eyes from 43 normal subjects or suspected/definite glaucoma patients were prospectively enrolled. All subjects had biometry with the IOLMaster and disc/retinal nerve fiber layer imaging with Cirrus SD-OCT (Optic Disc Cube 200×200) and Heidelberg Retina Tomograph (HRT). Uncorrected disc and rim areas and measurements corrected for eye magnification with Bennetts formula (AL-corrected measurements), along with 30° sectoral rim areas, vertical cup-to-disc ratio (VCDR), and cup volume, were compared between the two devices.nnnRESULTSnThe median (range) axial length (AL) was 24.2 mm (22.4-27.7 mm). Mean keratometry-corrected HRT disc area measurements were larger than AL-corrected HRT and SD-OCT measurements (P < 0.001 for both) and the difference was a function of keratometry measurements (K-readings). The AL-corrected HRT disc area and uncorrected/corrected Cirrus disc areas were not significantly different (P > 0.481). HRT rim area was larger than Cirrus measurements (P < 0.001) and the difference decreased with decreasing rim area. HRT VCDR and cup volume were significantly smaller than Cirrus measurements (P < 0.001). The correlations for sectoral rim areas between the two devices were moderate at best (intraclass correlation coefficients = 0.12-0.65).nnnCONCLUSIONSnHRT overestimated optic disc area as compared to SD-OCT. A portion of the difference in HRT and SD-OCT disc measurements is due to HRTs magnification correction algorithm. Rim area measurements from HRT were larger than from SD-OCT, likely a result of different definitions for the reference plane and differences in disc area measurements. Disc parameters from the two devices are not interchangeable.

Subretinal Transplantation of Embryonic Stem Cell-Derived Retinal Pigment Epithelium for the Treatment of Macular Degeneration: An Assessment at 4 Years.

Advanced macular degeneration is an important cause of vision loss in the United States with over 2 million people affected by the disease. Despite substantial progress in the development of new therapies for wet AMD, the severe visual impairment associated with geographic atrophy in dry AMD or Stargardt disease remains untreatable. Recently, two phase I/II studies involving 18 patients with these diseases have demonstrated that it is possible to safely implant human embryonic stem cell-derived RPE (hESC-RPE) in an attempt to rescue photoreceptors and visual function. The anatomical and functional results are encouraging, with more than half of treated patients experiencing sustained improvements in visual acuity and demonstrating evidence of possible cellular engraftment. However, any conclusions remain tempered by the relatively short follow-up time, lack of a formal control group, poor initial visual acuity, and small number of patients. Aside from an instance of postoperative infectious endophthalmitis, no adverse events related to the cell therapy, such as hyperproliferation, tumorigenicity, or rejection-related inflammation were noted in this initial cohort of 18 patients. These first-in-human safety studies have opened the door to future studies enrolling patients with less advanced disease, treating other diseases that result in RPE loss, employing shorter immunosuppressive regimens, and using alternative strategies for RPE transplantation such as sheets of cells with or without scaffolding to mimic Bruchs membrane. The ultimate goal of these initial safety studies is to promote continued translation of complex biological therapies into meaningful treatment strategies that may address unmet medical needs.

Measurement of the Optic Disc Vertical Tilt Angle With Spectral-Domain Optical Coherence Tomography and Influencing Factors

PURPOSEnTo report a novel method for measuring the vertical tilt angle of the optic nerve (ON) head and to investigate the associated factors.nnnDESIGNnCross-sectional diagnostic study.nnnMETHODSnOne hundred and twelve normal, glaucomatous, and glaucoma suspect eyes (99 patients) were enrolled in this study. Subjects underwent a full eye examination, biometry, and spectral-domain optical coherence tomography (SDOCT). The vertical tilt angle was measured on high-resolution cross-sectional SDOCT images passing through the ON head and foveal centers using the inner edges of the Bruch membrane opening as the reference plane. The correlation between the vertical tilt angle with the ovality index and the potential associated factors was estimated with univariate and multivariate linear regression analyses.nnnRESULTSnThe median (interquartile range, [IQR]) axial length and visual field mean deviation were 24.5 (23.8-25.3) mm and -0.9 (-2.76 to 0.26) dB. The median (IQR) tilt angle was 3.5 (1.2-11.2) degrees. There was a moderate correlation between the ovality index and tilt angle (Spearman ρ = 0.351; P < .001). In univariate analyses, axial length, spherical equivalent, and mean deviation were correlated with the tilt angle (P = .002, P = .011, and P = .013, respectively). Axial length, mean deviation, and their interaction showed a statistically significant correlation with the tilt angle in multivariate analyses (P = .044 for axial length, P = .039 for mean deviation, and P = .028 for their interaction).nnnCONCLUSIONSnWe describe a new method for measuring the ON head vertical tilt angle with high-resolution SDOCT imaging. The ovality index demonstrated only a moderate correlation with the tilt angle measurements and hence is not a good proxy measure for the vertical ON head tilt angle. Axial length and visual field mean deviation are the main factors associated with the ON head vertical tilt angle. The underlying basis for the relationship of vertical tilt angle and glaucoma severity should be further explored.

Preliminary results of subconjunctival bevacizumab in primary pterygium excision.

Purpose: To evaluate the efficacy of subconjunctival bevacizumab as an adjunctive therapy for primary pterygium surgery. Material and Methods: This randomized prospective clinical study was conducted on 30 eyes of 30 patients. After pterygium excision and accomplishing a rotational conjunctival flap, 15 patients (case group) received 1.25 mg (0.1 ml) bevacizumab, and 15 other patients (control group) received 0.1 ml balanced salt solution subconjunctivally. The main outcome measures were recurrence of pterygia, horizontal length of the corneal epithelial defect, conjunctival erythema, lacrimation and photophobia during the first postoperative week. Results: There were no statistically significant differences regarding age, sex or recurrence risk factors between the two groups (p > 0.05). The pterygia resolved in 13 (86.6%) of 15 eyes in both groups, with a recurrence rate of 13.4% during a mean follow-up period of 8 ± 1.4 months in the case group and 7.4 ± 1.5 months in the control group (p = 0.2). There were no statistically significant differences regarding reduction in refractive astigmatism, improvement in visual acuity, corneal epithelial defects, conjunctival erythema, lacrimation or photophobia between the case and control groups (p > 0.05). Conclusions: A single intraoperative subconjunctival bevacizumab injection had no effect on recurrence rate or early postoperative conjunctival erythema, lacrimation, photophobia or healing of corneal epithelial defects following pterygium excision.

Effect of intravitreal bevacizumab on retrobulbar blood flow in injected and uninjected fellow eyes of patients with neovascular age-related macular degeneration.

Background: To determine the effect of intravitreal administration of bevacizumab (1.25 mg/0.05 mL) on retrobulbar circulation of the injected and the fellow (uninjected) eyes in patients with neovascular age-related macular degeneration. Methods: In this prospective study, the retrobulbar hemodynamics of 43 patients with neovascular age-related macular degeneration was examined by color Doppler ultrasonography. Peak systolic velocity, end-diastolic velocity, and resistive index values in the central retinal artery and short posterior ciliary artery in both injected and uninjected fellow eyes were measured at baseline and 7 days after a single intravitreal injection of bevacizumab. Results: At baseline, the peak systolic velocity, end-diastolic velocity, and the resistive index in the central retinal artery and short posterior ciliary artery of the injected eye were not significantly different compared with the fellow uninjected eye (P > 0.05 for all). However, intravitreal bevacizumab induced a significant reduction in the peak systolic velocity and end-diastolic velocity and a significant rise in the resistive index of the central retinal artery and short posterior ciliary artery of the injected eye (P ⩽ 0.006 for all). Peak systolic velocity and end-diastolic velocity decreased in the central retinal artery (P = 0.023 and P = 0.030) and the short posterior ciliary artery (P = 0.001 and P < 0.000) in the uninjected eye while the resistive index did not significantly change in central retinal artery (P = 0.114) and short posterior ciliary artery (P = 0.082) of the fellow eyes. Conclusion: Intravitreal injection of bevacizumab significantly affects ocular hemodynamic parameters of both the injected and the uninjected fellow eyes with neovascular age-related macular degeneration.

Lamellar Macular Hole: Two Distinct Clinical Entities?

PURPOSEnTo investigate whether lamellar macular holes can be divided into different subgroups.nnnDESIGNnRetrospective observational case series.nnnMETHODSnIn this institutional study, clinical charts and spectral-domain optical coherence tomography (OCT) images of 102 eyes of 90 consecutive patients diagnosed with lamellar macular hole were reviewed. In OCT imaging, the presence of lamellar macular hole was defined according to the following findings: presence of irregular foveal contour, separation of the layers of the neurosensory retina, and the absence of full-thickness macular defect. Mean outcome was the morphologic andxa0functional characterization of different subtypes of macular hole.nnnRESULTSnTwo different subtypes of lamellar macular hole were identified: tractional and degenerative. The first type, tractional, was diagnosed in 43 eyes, and was characterized by the schitic separation of neurosensory retina between outer plexiform and outer nuclear layers. It often presented with an intact ellipsoid layer and was associated with tractional epiretinal membranes and/or vitreomacular traction. The second type, degenerative, was diagnosed in 48 eyes, and its distinctive traits included the presence of intraretinal cavitation that could affect all retinal layers. It was often associated with nontractional epiretinal proliferation and a retinal bump. Moreover, it often presented with early ellipsoidal zone defect and its pathogenesis, although chronic and progressive, remains poorly understood. Eleven eyes shared common features with both tractional and degenerative lamellar macular holes and were classified as mixed lesions.nnnCONCLUSIONSnDegenerative and tractional lamellar macular holes may be 2 distinct clinical entities. A revision of the current concept of lamellar macular holes is needed.

Deep anterior lamellar keratoplasty with melles technique for granular corneal dystrophy.

Purpose: The purpose of this study was to evaluate the clinical results of deep anterior lamellar keratoplasty (DALK) using the Melles technique in granular corneal dystrophy. Methods: Seven eyes from 5 patients who underwent DALK using Melles technique for granular corneal dystrophy were included in this study. The parameters evaluated included patients demographics, preoperative and postoperative best spectacle-corrected visual acuities (BSCVAs), and timing and pattern of recurrence. Results: The mean age of the patients was 37 ± 9.4 years (range 29-46 years) at the time of surgery. The mean length of follow-up (DALK to last visit) was 38.4 ± 18.6 months (range 10-63 months). The procedure was performed without any major complication in all eyes. Mean preoperative BSCVA was 20/220 (range 20/400 to 20/100), which improved to 20/27 (range 20/30 to 20/25) at 6 months after DALK. Mean BSCVA was 20/50 (range 20/400-20/20) at last follow-up. Simple recurrence occurred in 5 (71%) of 7 eyes. The mean time from surgery to recurrence was 15.6 ± 1.8 months (range 13-16 months). Clinically significant recurrences occurred 34 ± 2 months after the procedures in 3 (43%) of 7 eyes. Two (30%) of 7 eyes had no recurrence at all. Conclusions: Although granular corneal dystrophy is likely to recur after DALK, this technique can restore and preserve useful visual function for a significant period in these patients.

Pointwise rates of visual field progression cluster according to retinal nerve fiber layer bundles.

PURPOSEnTo explore whether pointwise rates of visual field progression group together in patterns consistent with retinal nerve fiber layer (RNFL) bundles.nnnMETHODSnThree hundred eighty-nine eyes of 309 patients from the Advanced Glaucoma Intervention Study with ≥6 years of follow-up and ≥12 reliable visual field exams were selected. Linear and exponential regression models were used to estimate pointwise rates of change over time. Clustering of pointwise rates of progression was investigated with hierarchical cluster analysis using Pearsons correlation coefficients as distance measure and an average linkage scheme for building the hierarchy with cutoff value of r > 0.7.nnnRESULTSnThe average mean deviation (±SD) was -10.9 (±5.4). The average (±SD) follow-up time and number of visual field exams were 8.1 (±1.1) years and 15.7 (±3.0), respectively. Pointwise rates of progression across the visual field grouped into clusters consistent with anatomic patterns of RNFL bundles with both linear (10 clusters) and exponential (six clusters) regression models. One hundred forty-four (37%) eyes progressed according to the two-omitting pointwise linear regression model.nnnCONCLUSIONSnointwise rates of change in glaucoma patients cluster into regions consistent with RNFL bundle patterns. This finding validates the clinical significance of such pointwise rates. The correlations among pointwise rates of change can be used for spatial filtering purposes, facilitating detection or prediction of glaucoma progression.

Anti-VEGF therapy with bevacizumab for anterior segment eye disease.

Purpose: To review the current literature concerning the use of bevacizumab in treating neovascular disorders affecting the anterior segment ocular structures. Methods: The authors reviewed the literature on anti–vascular endothelial growth factor (VEGF) therapy with bevacizumab for various anterior segment neovascular disorders that was indexed in MEDLINE (up to January 2011). Results: Response to bevacizumab anti-VEGF therapy is variable, based on the amount of scarring, the chronicity and extent of corneal neovascularization, the disease process, and the medication formulation and its route of administration. Anti-VEGF agents are especially effective when administered early, before anatomical changes, such as corneal neovascularization and/or angle closure, are established. Neovascularization can recur if the ischemic or inflammatory process is not reversed, so eyes with long-standing diseases, such as autoimmune disorders that involve ongoing inflammation and VEGF production, seem to be less responsive to bevacizumab anti-VEGF therapy. For established neovascularization, combining anti-VEGF agents with the removal of established vessels may be more effective than anti-VEGF therapy alone. Subconjunctival bevacizumab may be more appropriate for focal, deep, and peripheral neovascularization, whereas diffuse superficial neovascularization with central corneal involvement may be best treated via topical application. Conclusions: Besides the widely accepted use of bevacizumab in cancer therapy and chorioretinal neovascularization, the initial, striking, short-term response and patients high tolerance of local bevacizumab therapy offer encouraging results for the potential role of anti-VEGF agents in treating anterior segment neovascular disorders. Controlled prospective trials are needed to establish the long-term safety, efficacy, and dosing guidelines for the use of anti-VEGF agents in anterior segment neovascularization.