A comprehensive update on the use of optical coherence tomography angiography in glaucoma.

PURPOSE: The primary purpose of this review is to provide a comprehensive summary on the technical principles of OCTA and to enumerate vascular parameters being explicated for glaucoma diagnosis and progression with emphasis on recent studies. In addition, the authors also summarize the future clinical potentials of OCTA in glaucoma and enumerate the limitations of this imaging modality in the present-day scenario. METHODS: The index study is a narrative review on OCTA in glaucoma. The authors searched the PubMed database using the key phrases ''optical coherence tomography angiography" AND "glaucoma,'' AND/OR "vascular parameters" AND/OR "ocular perfusion." Being a relatively recent development in ocular imaging, studies in which OCTA imaging had been used for glaucoma evaluation since 2012 were included until March 2022. The literature search included original studies and previous review articles, while case reports were excluded. Preliminary search was based on relevant articles with search keywords in the title and abstract. The second screening was performed by reading the full text of the literature. RESULTS: Recent studies indicate reduction in microcirculation in glaucomatous eyes compared to the normal subjects. The area of interest for glaucoma evaluation using OCTA varies among the different studies. Based on the literature reviewed here, (1) OCTA parameters measured in the peripapillary; ONH and macular area have been shown to differentiate between glaucoma and normal eyes with a discriminatory power comparable to OCT parameters used routinely in clinics, (2) monitoring of peripapillary and macular vessel density may provide important information to the evaluation of glaucoma progression and prediction of rates of disease worsening, (3) studies suggest strong correlation between the OCTA parameters, the OCT parameters and visual function, measured by visual field testing, in glaucomatous eyes, (4) future prospects of OCTA in glaucoma evaluations using AI predicting structural and functional features and prognosis based on early vascular findings would open up scope for early detection of high-risk suspects and fast progressors in glaucoma. CONCLUSION: OCTA can be useful in quantifying vascular parameters in the optic disc, peripapillary and the macular regions for glaucoma evaluation. OCTA shows potential to become a part of everyday glaucoma management.

Novel combination therapy reduces subconjunctival fibrosis after glaucoma filtration surgery in the rabbit model.

BACKGROUND: Glaucoma filtration surgery (GFS) is limited by subconjunctival, episcleral and scleral fibrosis sealing the trabeculectomy and scarring the filtering bleb. Mitomycin-C (MMC) is commonly applied intraoperatively to the subconjunctival and/or intrascleral space to reduce scarring and promotes GFS success but is associated with postoperative scleral melting and bleb leaks. IP-10 peptide (IP-10p), an ELR-negative CXC chemokine mimetic and inhibitor of fibroblast function, may be an alternative or adjunct to current postoperative GFS treatments. This study sought to determine if IP-10p produces histological changes in tissue remodelling, vascularity and fibrosis that enhance bleb survival after GFS. METHODS: Rabbits underwent tube-assisted filtration surgery on the right eye with either: (a) IP-10p injected into bleb at time of surgery and postoperative days 2, 4 and 7, (b) intraoperative MMC or (c) intraoperative MMC plus IP-10p injected into bleb at time of surgery and postoperative days 2, 4 and 7. Left contralateral eyes were treated with balanced salt solution (BSS). RESULTS: IP-10p-treated blebs demonstrated reduced collagen deposition, cellularity and overall reduction of scar formation compared to BSS-control. Bleb vascularity was reduced compared to BSS-control and MMC treatment groups. Additionally, IP-10p/MMC treated eyes demonstrated an increased number of conjunctival goblet cells in bleb histology compared to the dramatic loss seen with MMC treatment alone. CONCLUSIONS: This study demonstrates that IP-10p significantly reduces histological scarring compared to BSS or MMC alone, does not damage the conjunctiva to the extent of current standards, and may be an alternative or adjunct to MMC for those undergoing GFS.

Five-year clinical outcomes of combined phacoemulsification and trabectome surgery at a single glaucoma center.

PURPOSE: To analyze the 5-year results of trabectome ab interno trabeculectomy of a single glaucoma center. METHOD: In this retrospective interventional single-center case series, data of 93 patients undergoing ab interno trabeculotomy between September 2010, and December 2012 were included. Kaplan-Meier analysis was performed using success criteria defined as postoperative intraocular pressure (IOP) ≤ 21 mmHg, and > 20% reduction from preoperative IOP, and no need for further glaucoma surgery. Risk factors for failure were identified using Cox proportional hazards ratio (HR). RESULTS: The retention rate for 5-year follow-up was 66%. The cumulative probability of success at 1, 2, 3, 4, and 5 years was 82.6%, 76.7%, 73.9%, 72.3%, and 67.5%. Risk factors for failure were lower baseline IOP (HR = 0.27, P = 0.001), younger age (HR = 0.25, P = 0.02), and higher central corneal thickness (HR = 0.18, P = 0.01). Exfoliative glaucoma was associated with a higher success rate (HR = 0.39, P = 0.02). IOP was decreased significantly from 20.0 ± 5.6 mmHg at baseline to 15.6 ± 4.6 mmHg at 5-year follow-up (P = 0.001). The baseline number of glaucoma medications was 1.8 ± 1.2, which decreased to 1.0 ± 1.2 medications at 5 years. CONCLUSION: Trabectome surgery was associated with a good long-term efficacy and safety profile in this single-center case series with a high retention rate.

28-day intraocular pressure reduction with a single dose of brimonidine tartrate-loaded microspheres.

Treatment of glaucoma by intraocular pressure (IOP) reduction is typically accomplished through the administration of eye drops, the difficult and frequent nature of which contributes to extremely low adherence rates. Poor adherence to topical treatment regimens in glaucoma patients can lead to irreversible vision loss and increased treatment costs. Currently there are no approved treatments for glaucoma that address the inherent inefficiencies in drug delivery and patient adherence. Brimonidine tartrate (BT), a common glaucoma medication, requires dosing every 8-12 h, with up to 97% of patients not taking it as prescribed. This study provides proof-of-principle testing of a controlled release BT formulation. BT was encapsulated in poly(lactic-co-glycolic) acid microspheres and drug release was quantified using UV-Vis spectroscopy. For in vivo studies, rabbits were randomized to receive a single subconjunctival injection of blank (no drug) or BT-loaded microspheres or twice daily topical 0.2% BT drops. The microspheres released an average of 2.1 ± 0.37 µg BT/mg microspheres/day in vitro. In vivo, the percent decrease in IOP from baseline was significantly greater in the treated eye for both topical drug and drug-loaded microspheres versus blank microspheres throughout the 4-week study, with no evidence of migration or foreign body response. IOP measurements in the contralateral, untreated eyes also suggested a highly localized effect from the experimental treatment. A treatment designed using the release systems described in this study would represent a vast improvement over the current clinical standard of 56-84 topical doses over 28 days.

Teleglaucoma Initiative at a Veterans Affairs Hospital: Pilot Safety Data and Early Experience.

PURPOSE: To evaluate the safety, reliability, and efficacy of telemedicine in delivering tertiary subspecialty glaucoma care (herein referred to as teleglaucoma) to the veteran patient population. DESIGN: Prospective case series. PARTICIPANTS: Twenty patients being referred for glaucoma subspecialist opinion participated in the pilot safety study. One hundred eighteen patients participated in the secondary study of the acceptability and service efficacy of teleglaucoma. METHODS: In the pilot study, safety was assessed by determining interobserver and intraobserver consistency (Krippendorff's α). This compared an in-person assessment by a glaucoma subspecialist with the remote assessment of 2 other glaucoma subspecialists (electronic health record alone reviewed). In the secondary study, teleglaucoma was implemented whereby testing and eye examination were carried out remotely by an optometrist or comprehensive ophthalmologist, and the clinical decision was made by the glaucoma subspecialist on review of the electronic health record alone. MAIN OUTCOME MEASURES: In the pilot study, interobserver and intraobserver consistency in making a diagnosis and treatment plan (acceptable, ≥ 0.80 Krippendorff's α). In the secondary study, patient satisfaction measured by survey, wait time for teleglaucoma opinion versus wait time for in-person opinion, and time spent on teleglaucoma consultations. RESULTS: Interobserver and intraobserver consistency showed an α of 0.86 and 0.92, respectively, for diagnosis, and 0.86 and 0.85, respectively, for treatment plan. In the secondary study, patient satisfaction was 4.55 of 5.00 (5 = maximum satisfaction; range, 3.28-4.93). Improved consultation lead time was demonstrated, with the median time for a doctor to respond to an electronic consultation being 3 days, versus 43 days for an in-person visit. Teleglaucoma also demonstrated positive benefits to the health care system by reducing the time doctors spent reviewing each patient's case (history, examination findings, imaging results, visual fields; 19 minutes for teleglaucoma consultation vs. 31 minutes for in-person evaluation). CONCLUSIONS: Decisions regarding diagnoses and treatment plans between in-person consultation and the teleglaucoma program showed high reliability. Patient satisfaction was high. Additional benefits were observed in wait time for subspecialty glaucoma opinion, efficient allocation of the doctor's time, and fiscal benefit to the health care system.

Sensory integration abilities for balance in glaucoma, a preliminary study.

The goal of this study was to quantify the association between sensory integration abilities relevant for standing balance and disease stage in glaucoma. The disease stage was assessed using both functional (visual field deficit) and structural (retinal nerve fiber layer thickness) deficits in the better and worse eye. Balance was assessed using an adapted version of the well-established Sensory Organization Test (SOT). Eleven subjects diagnosed with mild to moderate glaucoma stood for 3 min in 6 sensory challenging postural conditions. Balance was assessed using sway magnitude and sway speed computed based on center-of-pressure data. Mixed linear regression analyses were used to investigate the associations between glaucoma severity and balance measures. Findings revealed that the visual field deficit severity in the better eye was associated with increased standing sway speed. This finding was confirmed in eyes open and closed conditions. Balance was not affected by the extent of the visual field deficit in the worse eye. Similarly, structural damage in either eye was not associated with the balance measures. In summary, this study found that postural control performance was associated with visual field deficit severity. The fact that this was found during eyes closed as well suggests that reduced postural control in glaucoma is not entirely attributed to impaired peripheral visual inputs. A larger study is needed to further investigate potential interactions between visual changes and central processing changes contributing to reduced balance function and increased incidence of falls in adults with glaucoma.

Diffusion Tensor Imaging of Visual Pathway Abnormalities in Five Glaucoma Animal Models.

Purpose: To characterize the visual pathway integrity of five glaucoma animal models using diffusion tensor imaging (DTI). Methods: Two experimentally induced and three genetically determined models of glaucoma were evaluated. For inducible models, chronic IOP elevation was achieved via intracameral injection of microbeads or laser photocoagulation of the trabecular meshwork in adult rodent eyes. For genetic models, the DBA/2J mouse model of pigmentary glaucoma, the LTBP2 mutant feline model of congenital glaucoma, and the transgenic TBK1 mouse model of normotensive glaucoma were compared with their respective genetically matched healthy controls. DTI parameters, including fractional anisotropy, axial diffusivity, and radial diffusivity, were evaluated along the optic nerve and optic tract. Results: Significantly elevated IOP relative to controls was observed in each animal model except for the transgenic TBK1 mice. Significantly lower fractional anisotropy and higher radial diffusivity were observed along the visual pathways of the microbead- and laser-induced rodent models, the DBA/2J mice, and the LTBP2-mutant cats compared with their respective healthy controls. The DBA/2J mice also exhibited lower axial diffusivity, which was not observed in the other models examined. No apparent DTI change was observed in the transgenic TBK1 mice compared with controls. Conclusions: Chronic IOP elevation was accompanied by decreased fractional anisotropy and increased radial diffusivity along the optic nerve or optic tract, suggestive of disrupted microstructural integrity in both inducible and genetic glaucoma animal models. The effects on axial diffusivity differed between models, indicating that this DTI metric may represent different aspects of pathological changes over time and with severity.

Citicoline Modulates Glaucomatous Neurodegeneration Through Intraocular Pressure-Independent Control.

Glaucoma is a neurodegenerative disease that causes progressive, irreversible vision loss. Currently, intraocular pressure (IOP) is the only modifiable risk factor for glaucoma. However, glaucomatous degeneration may continue despite adequate IOP control. Therefore, there exists a need for treatment that protects the visual system, independent of IOP. This study sought, first, to longitudinally examine the neurobehavioral effects of different magnitudes and durations of IOP elevation using multi-parametric magnetic resonance imaging (MRI), optokinetics and histology; and, second, to evaluate the effects of oral citicoline treatment as a neurotherapeutic in experimental glaucoma. Eighty-two adult Long Evans rats were divided into six groups: acute (mild or severe) IOP elevation, chronic (citicoline-treated or untreated) IOP elevation, and sham (acute or chronic) controls. We found that increasing magnitudes and durations of IOP elevation differentially altered structural and functional brain connectivity and visuomotor behavior, as indicated by decreases in fractional anisotropy in diffusion tensor MRI, magnetization transfer ratios in magnetization transfer MRI, T1-weighted MRI enhancement of anterograde manganese transport, resting-state functional connectivity, visual acuity, and neurofilament and myelin staining along the visual pathway. Furthermore, 3 weeks of oral citicoline treatment in the setting of chronic IOP elevation significantly reduced visual brain integrity loss and visual acuity decline without altering IOP. Such effects sustained after treatment was discontinued for another 3 weeks. These results not only illuminate the close interplay between eye, brain, and behavior in glaucomatous neurodegeneration, but also support a role for citicoline in protecting neural tissues and visual function in glaucoma beyond IOP control.

Scleral-Sutured Intraocular Lens Dislocations Secondary to Eyelet Fractures.

OBJECTIVE: To report clinical features and visual outcomes following eyelet fractures of scleral-sutured enVista MX60 (Bausch + Lomb) intraocular lenses (IOL). DESIGN: Retrospective, multi-center, multi-surgeon, observational case series. METHODS: Study Population: Patients with scleral-sutured enVista MX60 IOLs that experienced either an intraoperative or post-operative eyelet fracture associated with dislocation or subluxation. PROCEDURES: All records were reviewed for patients with a dislocated or subluxed scleral-sutured enVista MX60 IOL. Clinical features and outcomes were gathered. Main Outcome Measures: Clinical setting, surgical technique, complications, and visual acuity. RESULTS: A total of 25 scleral-sutured enVista MX60 IOLs displacements secondary to eyelet fractures in 23 eyes of 23 patients were included. There were 20 IOLs that sustained a postoperative fracture and 5 IOLs that sustained an intraoperative fracture. Of the postoperative fractures, 7 were dislocated and 13 were subluxed. Gore-Tex was the suture of choice for 19 of the postoperative fractures and all 5 of the intraoperative fractures, and Prolene was used for 1 postoperative fracture. The mean time until postoperative fracture was 96 ± 125 days, and the median time was 61 (IQR 48-144) days. Of the postoperative fractures, new MX60s were sutured in 10 patients, and 2 of them experienced repeat displacements due to a new eyelet fracture. In the intraoperative fracture group, new MX60s were sutured in 4 patients and an Akreos AO60 lens was placed in the 5th patient. The mean preoperative best-corrected logMAR visual acuity for all patients improved from 1.2 ± 0.8 (20/317 Snellen equivalent) to 0.5 ± 0.5 (20/63 Snellen equivalent) at most recent follow-up after lens replacement. CONCLUSIONS: Scleral-sutured MX60 intraocular lenses can experience intraoperative or postoperative eyelet fractures, resulting in lens subluxation or dislocation. Surgeons should be aware of this complication when evaluating secondary intraocular lens options.

Comparative Outcomes of the Molteno3 and Baerveldt Glaucoma Implants.

PURPOSE: To compare outcomes between 2 nonvalved glaucoma drainage devices (GDDs) used to treat refractory glaucoma or in patients with neovascular/uveitic glaucoma likely to be poorly responsive to less aggressive therapies. DESIGN: Retrospective, nonrandomized, multicenter comparative study. PARTICIPANTS: A total of 117 eyes from 117 patients. METHODS: Retrospective chart review of patients who underwent implantation of the Baerveldt (BGI) (Abbott Medical Optics, Abbott Park, IL) or the Molteno3 glaucoma implant (MGI) (Molteno Ophthalmic Limited, Dunedin, New Zealand). Noninferiority of the MGI versus the BGI was tested with Cox and mixed-effects regression models. Interventions in each group were analyzed with chi-square tests. MAIN OUTCOME MEASURES: The primary outcome was time until device failure, defined as intraocular pressure (IOP) >21 mmHg or a reduction <20%, hypotony, reoperation for glaucoma, or loss of light perception. Secondary outcomes were intraoperative time, postoperative IOP, number of IOP-lowering medications, and visual acuity (VA). RESULTS: The MGI could not be deemed noninferior to the BGI with regard to time until device failure (hazard ratio [HR], 0.83; confidence interval [CI], 0.41-1.65). The MGI was noninferior to the BGI when comparing postoperative IOP, a difference of -0.40 mmHg (95% CI, -1.74-0.93). The MGI needed 2% fewer medications (ratio of 0.98, 95% CI, 0.79-1.22), but noninferiority could not be claimed. With regard to VA, the MGI's mean was 0.10 logarithm of the minimum angle of resolution (logMAR) higher (95% CI, -0.01-0.21), but noninferiority testing was again inconclusive. Intraoperative time for the MGI was 15.7 minutes shorter versus the 350 mm2 plate size BGI (P < 0.001) and 4.3 minutes shorter versus the 250 mm2 plate size BGI (P = 0.32). More patients in the MGI group needed secondary operative management (11%, P = 0.03). CONCLUSIONS: The MGI was noninferior to the BGI in lowering IOP. Differences in time until device failure, VA outcomes, and medication use were inconclusive. The MGI required more secondary operative interventions. The MGI required less time to implant than the BGI's 350 mm2 plate size implant. Overall, the use of both GDDs is justifiable to lower IOP when more conservative management has failed.

Injected Versus Sponge-Applied Mitomycin C (MMC) During Modified Trabeculectomy in New Zealand White Rabbit Model.

Purpose: Mitomycin C is routinely applied during trabeculectomy surgeries to enhance bleb survival after glaucoma filtration surgery. The current approach involves placing cellulose sponges soaked in mitomycin C at a standard concentration onto bare sclera for a predetermined duration, which varies among surgeons. The purpose of this study was to compare the effects of sponge-applied versus intra-Tenon injection of mitomycin C during modified trabeculectomy. Methods: Two groups of five New Zealand White rabbits underwent glaucoma filtration surgery with either preoperative intra-Tenon injection of mitomycin C or intraoperative application of mitomycin C using a cellulose sponge. Postoperative intraocular pressure was recorded weekly, and eyes were enucleated and sent for pathological examination and histological analysis. Results: An intra-Tenon injection of mitomycin C resulted in decreased intraocular pressure measurements and bleb vascularity compared to the controls but increased levels compared to the sponge-applied group. Collagen deposition and cellularity were reduced and the goblet cell population was increased in the intra-Tenon injection group. Conclusions: This study shows that an intra-Tenon injection can be an effective method for administering mitomycin C compared to the standard-of-care approach of mitomycin C being sponge applied onto bare sclera. Mitomycin C injection led to a greater reduction in intraocular pressure and inhibition of fibroblasts. The associated goblet cell population that can lead to increased mitomycin C toxicity-related morbidity was minimized with the intra-Tenon injection compared to the sponge-applied MMC treatment. Therefore, patients with ocular surface disease may benefit from an intra-Tenon injection. Translational Relevance: This project provides a direct, qualitative assessment in an animal model of common techniques within glaucoma filtration surgery for drug delivery to improve surgical success.

Scleral Fixation of Intraocular Lenses with Gore-Tex Suture: Refractive Outcomes and Comparison of Lens Power Formulas.

PURPOSE: To report refractive outcomes of scleral-fixated intraocular lens (IOL) implantation with Gore-Tex (W.L. Gore & Associates, Newark, DE) suture and combined pars plana vitrectomy and compare predicted refractive outcomes among 5 IOL power calculation formulas. DESIGN: Retrospective case series. PARTICIPANTS: Patients undergoing scleral-fixated IOL implantation with Gore-Tex suture at our institution between January 2015 and June 2018. METHODS: Comparison of preoperative biometrics with postoperative refraction and calculation of predicted refractive outcome with 5 different IOL formulas. MAIN OUTCOME MEASURES: Prediction error and absolute error to compare postoperative refraction with refraction predicted by lens power calculation formulas. RESULTS: Thirty-one eyes of 31 patients were included. All power calculations assumed in-the-bag position of the IOL. The Akreos A060 (Bausch & Lomb, Rochester, NY) was implanted in 23 eyes and the CZ70BD (Alcon, Fort Worth, TX) in 8 eyes, and all lenses were sutured 3 mm behind the limbus. Average postoperative spherical equivalent (SE) was -0.79±0.95 diopters (D). Average prediction error (postoperative SE refraction minus target refraction) was -0.19±0.72 D. Postoperative SE was within 1.0 D of target in 25 of 31 patients (81%) and 2.0 D of target in 31 of 31 patients (100%). The repeated-measures analysis of variance of absolute error by lens power formula was significant (P = 0.012), with Haigis demonstrating greater error. There was no significant difference among Barrett II, Sanders-Retzlaff-Kraff theoretical (SRK/T), Holladay 2, or Hoffer Q. CONCLUSIONS: For eyes undergoing pars plana vitrectomy with scleral-sutured IOL implantation, assumption of in-the-bag IOL position when calculating lens power leads to acceptable refractive outcomes. Barrett II, SRK/T, Holladay 2, and Hoffer Q formulas were noninferior to each other.

Author Correction: Matrix-bound nanovesicles prevent ischemia-induced retinal ganglion cell axon degeneration and death and preserve visual function.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Matrix-bound nanovesicles prevent ischemia-induced retinal ganglion cell axon degeneration and death and preserve visual function.

Injury to retinal ganglion cells (RGC), central nervous system neurons that relay visual information to the brain, often leads to RGC axon degeneration and permanently lost visual function. Herein this study shows matrix-bound nanovesicles (MBV), a distinct class of extracellular nanovesicle localized specifically to the extracellular matrix (ECM) of healthy tissues, can neuroprotect RGCs and preserve visual function after severe, intraocular pressure (IOP) induced ischemia in rat. Intravitreal MBV injections attenuated IOP-induced RGC axon degeneration and death, protected RGC axon connectivity to visual nuclei in the brain, and prevented loss in retinal function as shown by histology, anterograde axon tracing, manganese-enhanced magnetic resonance imaging, and electroretinography. In the optic nerve, MBV also prevented IOP-induced decreases in growth associated protein-43 and IOP-induced increases in glial fibrillary acidic protein. In vitro studies showed MBV suppressed pro-inflammatory signaling by activated microglia and astrocytes, stimulated RGC neurite growth, and neuroprotected RGCs from neurotoxic media conditioned by pro-inflammatory astrocytes. Thus, MBV can positively modulate distinct signaling pathways (e.g., inflammation, cell death, and axon growth) in diverse cell types. Since MBV are naturally derived, bioactive factors present in numerous FDA approved devices, MBV may be readily useful, not only experimentally, but also clinically as immunomodulatory, neuroprotective factors for treating trauma or disease in the retina as well as other CNS tissues.

Widespread brain reorganization perturbs visuomotor coordination in early glaucoma.

Glaucoma is the world's leading cause of irreversible blindness, and falls are a major public health concern in glaucoma patients. Although recent evidence suggests the involvements of the brain toward advanced glaucoma stages, the early brain changes and their clinical and behavioral consequences remain poorly described. This study aims to determine how glaucoma may impair the brain structurally and functionally within and beyond the visual pathway in the early stages, and whether these changes can explain visuomotor impairments in glaucoma. Using multi-parametric magnetic resonance imaging, glaucoma patients presented compromised white matter integrity along the central visual pathway and around the supramarginal gyrus, as well as reduced functional connectivity between the supramarginal gyrus and the visual occipital and superior sensorimotor areas when compared to healthy controls. Furthermore, decreased functional connectivity between the supramarginal gyrus and the visual brain network may negatively impact postural control measured with dynamic posturography in glaucoma patients. Taken together, this study demonstrates that widespread structural and functional brain reorganization is taking place in areas associated with visuomotor coordination in early glaucoma. These results implicate an important central mechanism by which glaucoma patients may be susceptible to visual impairments and increased risk of falls.

Treatment Outcomes of Mitomycin C-Augmented Trabeculectomy, Sub-Tenon Injection versus Soaked Sponges, after 3 Years of Follow-up: A Randomized Clinical Trial.

PURPOSE: To report the 3-year outcome of trabeculectomy with mitomycin C (MMC)-soaked sponges versus intra-Tenon injection of MMC in eyes with uncontrolled primary open-angle glaucoma. DESIGN: Randomized clinical trial. PARTICIPANTS: Eighty-two consecutive patients with uncontrolled primary open-angle glaucoma. METHODS: Participants were randomized either to intra-Tenon injection of 0.1 ml of 0.01% MMC (TI group) or 0.02% subconjunctival application of MMC-soaked sponges (TS group). Patients were followed up for 3 years after surgery. The data for 73 eyes were included in the final analysis. MAIN OUTCOME MEASURES: The primary outcome measure was the surgical success, defined as intraocular pressure (IOP) more than 5 mmHg and <21 mmHg, and IOP reduction of 20% or more from baseline, no reoperation for glaucoma, and no loss of light perception vision. Secondary outcome measures were IOP, glaucoma medications, best-corrected visual acuity (VA), bleb morphologic features according to the Indiana Bleb Appearance Grading Scale, complications, and endothelial cell count changes. RESULTS: The cumulative probability of success at 3-year follow-up was 72.2% in the TI group and 65.1% in the TS group (P = 0.30). Uncontrolled IOP was the most common reason for failure. The mean preoperative IOP was 22.4±4.6 mmHg with an average of 3.1±1.0 medications. At 3 years, final IOP was 15.3±3.7 mmHg in the TI group and 16.4±3.5 mmHg in the TS group (P = 0.55). Mean glaucoma number of medications was 0.9±1.1 and 1.1±1.1 in the TI and TS groups, respectively (P = 0.54). Blebs tended to be more diffuse (P = 0.032), less vascularized (P = 0.013), and more shallow (P = 0.012) after intra-Tenon injection. Visual outcomes and endothelial cell changes were similar in both groups (P = 0.47 and P = 0.94, respectively). CONCLUSIONS: Although the success rate and IOP reduction were comparable with both techniques, bleb morphologic parameters were more favorable after intra-Tenon injection of 0.1 ml of 0.01% MMC.

Eye dominance predicts fMRI signals in human retinotopic cortex.

There have been many attempts to define eye dominance in normal subjects, but limited consensus exists, and relevant physiological data is scarce. In this study, we consider two different behavioral methods for assignment of eye dominance, and how well they predict fMRI signals evoked by monocular stimulation. Sighting eye dominance was assessed with two standard tests, the Porta Test, and a 'hole in hand' variation of the Miles Test. Acuity dominance was tested with a standard eye chart and with a computerized test of grating acuity. We found limited agreement between the sighting and acuity methods for assigning dominance in our individual subjects. We then compared the fMRI response generated by dominant eye stimulation to that generated by non-dominant eye, according to both methods, in 7 normal subjects. The stimulus consisted of a high contrast hemifield stimulus alternating with no stimulus in a blocked paradigm. In separate scans, we used standard techniques to label the borders of visual areas V1, V2, V3, VP, V4v, V3A, and MT. These regions of interest (ROIs) were used to analyze each visual area separately. We found that percent change in fMRI BOLD signal was stronger for the dominant eye as defined by the acuity method, and this effect was significant for areas located in the ventral occipital territory (V1v, V2v, VP, V4v). In contrast, assigning dominance based on sighting produced no significant interocular BOLD differences. We conclude that interocular BOLD differences in normal subjects exist, and may be predicted by acuity measures.

Intraoperative Optical Coherence Tomography-Assisted Descemet Stripping Automated Endothelial Keratoplasty for Anterior Chamber Fibrous Ingrowth.

PURPOSE: Here, we present the first reported case of intraoperative optical coherence tomography (OCT)-assisted Descemet membrane stripping automated endothelial keratoplasty (DSAEK) in a patient with anterior segment fibrous ingrowth. METHODS: A 61-year-old woman with corneal edema and chronic angle-closure glaucoma secondary to fibrous ingrowth after 2 glaucoma shunt device implantations underwent dissection and removal of anterior chamber fibrous ingrowth and DSAEK. The surgical techniques using intraoperative OCT and outcome are described. RESULTS: Intraoperative OCT provided a clear dissection plane of the fibrous membranes in the anterior chamber and view of their relation to the iris and corneal endothelium, despite an opacified cornea. The placement of the donor lenticule and absence of interface fluid were also verified intraoperatively. The postoperative course was uncomplicated with satisfactory outcome. CONCLUSIONS: We conclude that intraoperative OCT is a useful tool during DSAEK surgery, particularly in complicated cases such as anterior segment fibrous ingrowth and significant corneal edema.

Long Term Glaucoma Drug Delivery Using a Topically Retained Gel/Microsphere Eye Drop.

The purpose of this study was to characterize and determine the efficacy of a long-term, non-invasive gel/microsphere (GMS) eye drop for glaucoma. This novel drug delivery system is comprised of a thermoresponsive hydrogel carrier and drug-loaded polymer microspheres. In vitro release of brimonidine from the GMS drops and gel properties were quantified. A single brimonidine-loaded GMS drop was administered to 5 normotensive rabbits and intraocular pressure (IOP) was monitored for 28 days. Here we report that IOP reduction in rabbits receiving a single brimonidine GMS drop was comparable to that of rabbits receiving twice daily, standard brimonidine drops. GMS drops were retained in the inferior fornix in all animals for the length of the study. Our results suggest in vivo efficacy over 28 days from a single GMS drop and a potential decrease in systemic absorption, based on a lack of substantial IOP effects on the fellow untreated eye, compared to brimonidine twice-daily eye drops. To our knowledge, this represents the first long-term, drug-releasing depot that can be administered as a traditional eye drop.

Relating binocular and monocular vision in strabismic and anisometropic amblyopia.

OBJECTIVES: To examine deficits in monocular and binocular vision in adults with amblyopia and to test the following 2 hypotheses: (1) Regardless of clinical subtype, the degree of impairment in binocular integration predicts the pattern of monocular acuity deficits. (2) Subjects who lack binocular integration exhibit the most severe interocular suppression. METHODS: Seven subjects with anisometropia, 6 subjects with strabismus, and 7 control subjects were tested. Monocular tests included Snellen acuity, grating acuity, Vernier acuity, and contrast sensitivity. Binocular tests included Titmus stereo test, binocular motion integration, and dichoptic contrast masking. RESULTS: As expected, both groups showed deficits in monocular acuity, with subjects with strabismus showing greater deficits in Vernier acuity. Both amblyopic groups were then characterized according to the degree of residual stereoacuity and binocular motion integration ability, and 67% of subjects with strabismus compared with 29% of subjects with anisometropia were classified as having "nonbinocular" vision according to our criterion. For this nonbinocular group, Vernier acuity is most impaired. In addition, the nonbinocular group showed the most dichoptic contrast masking of the amblyopic eye and the least dichoptic contrast masking of the fellow eye. CONCLUSION: The degree of residual binocularity and interocular suppression predicts monocular acuity and may be a significant etiological mechanism of vision loss.