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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.

The primary aim was to determine if somatosensory impairments alter the association between falls history and glaucoma severity. A secondary aim was to identify the activities of daily living that cause increased concern related to falling in glaucoma and their association with glaucoma severity. Established questionnaires about falls and fear of falling (FoF) were mailed to participants diagnosed with glaucoma. Ninety-eight participants responded. Self-reported feet numbness and tingling symptoms were used to determine the presence of somatosensory impairments. Self-reported falls in glaucoma are associated with visual field deficits in both eyes, particularly in the presence of somatosensory impairments. In addition, increased FoF levels are linked with worse visual field deficits in both eyes, especially when performing challenging walking tasks. Somatosensory impairments alter the relationship between falls risk and visual field deficits in glaucoma. This information may be helpful in identifying older workers at an increased risk of falling.

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.

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.

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.

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-021-01033-6.

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.Prospective case series.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.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.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.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).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.

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.

Purpose To compare the efficacy and safety of the graft-free short tunnel small flap (STSF) technique with that of the scleral patch graft (SPG) in Ahmed glaucoma valve (AGV) (New World Medical Inc, Rancho Cucamonga, CA) implantation. Design Randomized clinical trial. Participants A total of 203 eyes of 203 patients with medically uncontrolled glaucoma, including 102 in the STSF group and 101 in the SPG group. Methods Patients were enrolled and assigned randomly to STSF or SPG. Main Outcome Measures Tube exposure, intraocular pressure (IOP), number of glaucoma medications, best-corrected visual acuity, surgical complications, and success rate (defined as IOP >5 mmHg, ≤21 mmHg, and IOP reduction ≥20% from baseline at 2 consecutive visits after 3 months, no reoperation for glaucoma). Results Only 1 patient in the SPG group developed tube exposure at 1-year follow-up. The cumulative probability of success during the first year of follow-up was 70% in the STSF group and 65% in the SPG group (P = 0.36). The IOP decreased significantly from 29.6±8.6 mmHg at baseline to 16.4±3.6 mmHg at the final follow-up in the STSF group (P = 0.001). The corresponding numbers for the SPG group were 30.9±11.2 and 15.8±4.7, respectively (P = 0.001). The final IOP was comparable between both groups (P = 0.65). Mean ± standard deviation of the number of glaucoma medications was 1.8±0.9 in the STSF group and 1.6±0.9 in the SPG group at final follow-up (P = 0.32). Postoperative complications developed in 8 patients (19%) in the STSF group and 9 patients (23%) in the SPG group (P = 0.81). Conclusions The STSF and SPG techniques had a comparable complication rate at the 1-year follow-up. Both techniques were comparable in terms of success rate, postoperative IOP, and glaucoma medications.

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.

Purpose: The purpose of this article is to examine the clinical outcomes of scleral fixation of intraocular lenses (IOLs) using Gore-Tex suture at our institution. Methods: A retrospective chart review was conducted of patients who underwent scleral fixation of an IOL with Gore-Tex suture with concurrent pars plana vitrectomy. Intraoperative and postoperative complications were assessed. Results: Seventy-four eyes of 74 patients were included with a mean follow-up interval of 210 days (range, 33–720 days). The mean best-corrected visual acuity improved from 20/480 (1.38 logarithm of the minimum angle of resolution [logMAR]) preoperatively to 20/78 (0.59 logMAR) postoperatively ( P < .001). Indications included dislocated lens implant (42), aphakia without capsular support (18), and subluxation of crystalline lens (14). Bausch and Lomb Akreos AO60 IOL was implanted in 52 eyes, Alcon CZ70BD in 15, and Bausch and Lomb enVista MX60 in 6. Postoperative complications included temporary ocular hypertension in 9 eyes (12%), temporary hypotony in 7 (9%), cystoid macular edema in 3 eyes (4%), corneal decompensation in 2 eyes (3%), IOL dislocation requiring exchange in 1 case (1.4%), vitreous hemorrhage in 2 cases (3%), and retinal detachment in 2 cases (3%). There were no cases of postoperative suture breakage or erosion, endophthalmitis, or hyphema. Conclusions: The use of Gore-Tex suture in scleral fixation of posterior chamber IOLs was well tolerated at a mean follow-up interval of 210 days. There were no suture-related complications.

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 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.

Central nervous system (CNS) neurons fail to regrow injured axons, often resulting in permanently lost neurologic function. Tacrolimus is an FDA-approved immunosuppressive drug with known neuroprotective and neuroregenerative properties in the CNS. However, tacrolimus is typically administered systemically and blood levels required to effectively treat CNS injuries can lead to lethal, off-target organ toxicity. Thus, delivering tacrolimus locally to CNS tissues may provide therapeutic control over tacrolimus levels in CNS tissues while minimizing off-target toxicity. Herein we show an electrospun poly(ester urethane) urea and tacrolimus elastomeric matrix (PEUU-Tac) can deliver tacrolimus trans-durally to CNS tissues. In an acute CNS ischemia model in rat, the optic nerve (ON) was clamped for 10s and then PEUU-Tac was used as an ON wrap and sutured around the injury site. Tacrolimus was detected in PEUU-Tac wrapped ONs at 24 h and 14 days, without significant increases in tacrolimus blood levels. Similar to systemically administered tacrolimus, PEUU-Tac locally decreased glial fibrillary acidic protein (GFAP) at the injury site and increased growth associated protein-43 (GAP-43) expression in ischemic ONs from the globe to the chiasm, consistent with decreased astrogliosis and increased retinal ganglion cell (RGC) axon growth signaling pathways. These initial results suggest PEUU-Tac is a biocompatible elastic matrix that delivers bioactive tacrolimus trans-durally to CNS tissues without significantly increasing tacrolimus blood levels and off-target toxicity., Highlights • PEUU-Tac locally delivers tacrolimus to CNS tissues • PEUU-Tac positively modulates CNS tissue remodeling • PEUU-Tac minimizes off-target tacrolimus toxicity Central nervous system (CNS) injury typically results in permanently lost neurological function. Tacrolimus is an FDA-approved drug used during organ transplantation that also has CNS neuroprotective and neuroregenerative properties. However, tacrolimus is typically delivered systemically in the blood and delivering effective concentrations to CNS tissues requires tacrolimus blood levels that can lead to adverse side effects in multiple organs. Herein we show that PEUU-Tac, a tacrolimus-eluting matrix, can locally deliver tacrolimus to injured CNS tissues without increasing blood levels, suggesting PEUU-Tac can be used to treat CNS injuries locally while minimizing adverse side effects.

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 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 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.

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.

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.

To report refractive outcomes of scleral-fixated intraocular lens (IOL) implantation with Gore-Tex (W.L. GoreAssociates, Newark, DE) suture and combined pars plana vitrectomy and compare predicted refractive outcomes among 5 IOL power calculation formulas.Retrospective case series.Patients undergoing scleral-fixated IOL implantation with Gore-Tex suture at our institution between January 2015 and June 2018.Comparison of preoperative biometrics with postoperative refraction and calculation of predicted refractive outcome with 5 different IOL formulas.Prediction error and absolute error to compare postoperative refraction with refraction predicted by lens power calculation formulas.Thirty-one eyes of 31 patients were included. All power calculations assumed in-the-bag position of the IOL. The Akreos A060 (BauschLomb, 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.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.

Purpose: To compare the efficacy and safety of graft-free short tunnel small flap (STSF) technique with that of scleral patch graft (SPG) in Ahmed glaucoma valve (AGV) implantation. Design: Randomized clinical trial. Participants: Eighty-eyes of eighty patients with medically uncontrolled glaucoma including 41 in STSF and 39 eyes in SPG. Methods: Patients were enrolled and assigned randomly to STSF or SPG. Main Outcome Measures: tube exposure, Intraocular pressure (IOP), number of glaucoma medications, best corrected visual acuity (BCVA), surgical complications, and success rate ( defined as intraocular pressure (IOP) >5 mmHg, ≤21 mmHg, and IOP reduction ≥20% from baseline at two consecutive visits after three months, no reoperation for glaucoma). Results: only one case in SPG developed tube exposure at 1-year follow-up. The cumulative probability of success during the first year of follow-up was 70% in the STSF and 65% in SPG (P = 0.36). IOP decreased significantly from 29.6 ± 8.6 mmHg at baseline to 16.4 ± 3.6 mmHg at the final follow-up in STSF (p = 0.001). The corresponding numbers for SPG were 30.9 ± 11.2 and 15.8 ± 4.7, respectively (p = 0.001). The final IOP was comparable between both groups (p = 0.65). Mean ± standard deviation of the number of glaucoma medications was 1.8 ± 0.9 in STSF and 1.6 ± 0.9 in SPG at final follow-up (P = 0.32). Postoperative complications developed in 8 patients (19%) in STSF and 9 patients (23%) in SPG (P = 0.81). Conclusions: STSF and SPG techniques had comparable complication rate at one-year follow-up. Both techniques were comparable in terms of success rate, postoperative IOP, and glaucoma medications.

Purpose: To analyze the five-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 mm Hg, or >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 five years 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). Pseudoexfoliation 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. A higher baseline IOP, older age, thinner cornea, and pseudoexfoliation glaucoma were associated with a higher success rate.

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.Randomized clinical trial.Eighty-two consecutive patients with uncontrolled primary open-angle glaucoma.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.The primary outcome measure was the surgical success, defined as intraocular pressure (IOP) more than 5 mmHg and21 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.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).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.

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.

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.

Human visual performance has been observed to show superiority in localized regions of the visual field across many classes of stimuli. However, the underlying neural mechanisms remain unclear. This study aims to determine whether the visual information processing in the human brain is dependent on the location of stimuli in the visual field and the corresponding neuroarchitecture using blood-oxygenation-level-dependent functional MRI (fMRI) and diffusion kurtosis MRI, respectively, in 15 healthy individuals at 3 T. In fMRI, visual stimulation to the lower hemifield showed stronger brain responses and larger brain activation volumes than the upper hemifield, indicative of the differential sensitivity of the human brain across the visual field. In diffusion kurtosis MRI, the brain regions mapping to the lower visual field showed higher mean kurtosis, but not fractional anisotropy or mean diffusivity compared with the upper visual field. These results suggested the different distributions of microstructural organization across visual field brain representations. There was also a strong positive relationship between diffusion kurtosis and fMRI responses in the lower field brain representations. In summary, this study suggested the structural and functional brain involvements in the asymmetry of visual field responses in humans, and is important to the neurophysiological and psychological understanding of human visual information processing.

The microstructural organization and composition of the corneoscleral shell (CSS) determine the biomechanical behavior of the eye, and are important in diseases such as glaucoma and myopia. However, limited techniques can assess these properties globally, non-invasively and quantitatively. In this study, we hypothesized that multi-modal magnetic resonance imaging (MRI) can reveal the effects of biomechanical or biochemical modulation on CSS. Upon intraocular pressure (IOP) elevation, CSS appeared hyperintense in both freshly prepared ovine eyes and living rat eyes using T2-weighted MRI. Quantitatively, transverse relaxation time (T2) of CSS increased non-linearly with IOP at 0–40 mmHg and remained longer than unloaded tissues after being unpressurized. IOP loading also increased fractional anisotropy of CSS in diffusion tensor MRI without apparent change in magnetization transfer MRI, suggestive of straightening of microstructural fibers without modification of macromolecular contents. Lastly, treatments with increasing glyceraldehyde (mimicking crosslinking conditions) and chondroitinase-ABC concentrations (mimicking glycosaminoglycan depletion) decreased diffusivities and increased magnetization transfer in cornea, whereas glyceraldehyde also increased magnetization transfer in sclera. In summary, we demonstrated the changing profiles of MRI contrast mechanisms resulting from biomechanical or biochemical modulation of the eye non-invasively. Multi-modal MRI may help evaluate the pathophysiological mechanisms in CSS and the efficacy of corneoscleral treatments.

Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease.

Amblyopia is a developmental visual disorder associated with loss of monocular acuity and sensitivity as well as profound alterations in binocular integration. Abnormal connections in visual cortex are known to underlie this loss, but the extent to which these abnormalities are regionally or retinotopically specific has not been fully determined. This functional magnetic resonance imaging (fMRI) study compared the retinotopic maps in visual cortex produced by each individual eye in 19 adults (7 esotropic strabismics, 6 anisometropes and 6 controls). In our standard viewing condition, the non-tested eye viewed a dichoptic homogeneous mid-level grey stimulus, thereby permitting some degree of binocular interaction. Regions-of-interest analysis was performed for extrafoveal V1, extrafoveal V2 and the foveal representation at the occipital pole. In general, the blood oxygenation level-dependent (BOLD) signal was reduced for the amblyopic eye. At the occipital pole, population receptive fields were shifted to represent more parafoveal locations for the amblyopic eye, compared with the fellow eye, in some subjects. Interestingly, occluding the fellow eye caused an expanded foveal representation for the amblyopic eye in one early–onset strabismic subject with binocular suppression, indicating real-time cortical remapping. In addition, a few subjects actually showed increased activity in parietal and temporal cortex when viewing with the amblyopic eye. We conclude that, even in a heterogeneous population, abnormal early visual experience commonly leads to regionally specific cortical adaptations.

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.

Excitotoxicity has been linked to the pathogenesis of several ocular diseases and injuries such as retinal ischemia,1–5 traumatic injury,6,7 glaucoma,8–11 and diabetic retinopathy.12,13 In the retina, the retinal ganglion cells preferentially express N-methyl-D-aspartate (NMDA)-type glutamate receptors and are believed to play a major role in glutamate excitotoxic retinal injury.14,15 While the cell bodies in the retina are commonly regarded as the primary site of insult, recent studies have suggested the early involvement of white matter degeneration in the posterior visual pathway after glutamate excitotoxicity in the eye.16–19 Nevertheless, because of limited noninvasive techniques available for assessing the visual pathways, the spatiotemporal patterns of neurodegenerative events in the visual system and their relationships with excitotoxic retinal injury in the eye are not fully elucidated. This in part hinders the development of effective strategies for disease monitoring and treatment. Magnetic resonance imaging (MRI) allows noninvasive, longitudinal, and multiparametric assessments of the visual system without depth limitation.20–25 Although there were existing MR reports assessing the effects of NMDA-induced excitotoxicity in developing and adult brain tissues,26,27 most of the neuropathy models employed did not differentiate clearly the locations of the primary site of insult or the initial events in white matter degeneration. In addition, the early MRI studies assessing visual system injury28,29 mainly used the conventional anatomical T2-weighted imaging or diffusion weighted imaging techniques at low magnetic field strengths with relatively limited sensitivity and specificity to characterize the underlying pathophysiological events. In this study, we employed the advanced MR techniques, namely diffusion tensor MRI (DTI) and manganese-enhanced MRI (MEMRI) at a high magnetic field strength, in combination with spectral-domain optical coherence tomography (OCT), with an aim to develop an in vivo model system for characterizing the spatiotemporal patterns of white matter integrity changes in the visual system and their relations to retinal integrity after glutamate excitotoxicity in the eye. Diffusion tensor MRI has been recently shown to reveal white matter integrity in normal, developing and diseased visual systems in rodent models under high magnetic field strengths.30–35 In particular, the measurements of water diffusion parallel and perpendicular to the nerve fibers have been suggested to be sensitive to axonal and myelin integrity respectively.31,36 Since intravitreal injection of NMDA has been commonly used as an experimental model to induce glutamate excitotoxic retinal ganglion cell death,37,38 in this study, we quantified the spatiotemporal DTI profiles in the rodent visual system with a 9.4 Tesla MRI scanner after NMDA-induced excitotoxic retinal injury. In addition, DTI results were compared with OCT measurement of the thickness of the retina and MEMRI of the anterograde transport along the visual pathway, in order to determine the eye–brain relationships and to correlate between structural and physiological characteristics in the injured visual system. As the retinal ganglion cells and the sites of toxic insult after intravitreal NMDA injection in the eye are physically isolated from the axons beyond the eye in the brain's visual system, our MRI and OCT studies in this NMDA model of retinal injury are well suited for providing information about the effects of excitotoxic perikaryal injury on white matter integrity changes in both ocular diseases and other neuropathies. Our cross-sectional and longitudinal results from these in vivo multidisciplinary ophthalmic imaging techniques may allow better monitoring of the disease progression in the visual system, and provide a platform for assessing treatment effects on both the eye and the visual pathway in future studies.

We report 4 cases of acute corneal edema with subsequent thinning and hyperopic shift following routine selective laser trabeculoplasty (SLT) for the treatment of primary open-angle glaucoma. Four women from 3 clinical sites developed acute corneal edema and haze within 2 days of uneventful SLT. In the following weeks to months, all treated corneas thinned to below pre-procedure thicknesses with resultant hyperopic shifts of nearly 2.0 diopters (D) to greater than 6.0 D. All eyes were moderately to highly myopic prior to SLT (spherical equivalent from −5.00 to −12.5 D). The corrected distance visual acuity 6 to 11 months after SLT was within 2 Snellen lines of the pre-procedure acuity in all patients; 2 patients required contact lenses. Corneal edema with subsequent corneal thinning and resultant hyperopic shift is an uncommon but possibly underrecognized complication of SLT, the etiology of which remains unknown but may be associated with moderate to high myopia. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

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.

Amblyopia is a developmental visual disorder associated with loss of monocular acuity and sensitivity as well as profound alterations in binocular integration. Abnormal connections in visual cortex are known to underlie this loss, but the extent to which these abnormalities are regionally or retinotopically specific has not been fully determined. This functional magnetic resonance imaging (fMRI) study compared the retinotopic maps in visual cortex produced by each individual eye in 19 adults (7 esotropic strabismics, 6 anisometropes and 6 controls). In our standard viewing condition, the non-tested eye viewed a dichoptic homogeneous mid-level grey stimulus, thereby permitting some degree of binocular interaction. Regions-of-interest analysis was performed for extrafoveal V1, extrafoveal V2 and the foveal representation at the occipital pole. In general, the blood oxygenation level-dependent (BOLD) signal was reduced for the amblyopic eye. At the occipital pole, population receptive fields were shifted to represent more parafoveal locations for the amblyopic eye, compared with the fellow eye, in some subjects. Interestingly, occluding the fellow eye caused an expanded foveal representation for the amblyopic eye in one early–onset strabismic subject with binocular suppression, indicating real-time cortical remapping. In addition, a few subjects actually showed increased activity in parietal and temporal cortex when viewing with the amblyopic eye. We conclude that, even in a heterogeneous population, abnormal early visual experience commonly leads to regionally specific cortical adaptations.

Amblyopia, sometimes called “lazy eye,” is a relatively common developmental visual disorder well characterized behaviorally; however, the neural substrates associated with amblyopia in humans remain unclear. We hypothesized that abnormalities in the cerebral cortex of subjects with amblyopia exist, possibly as a result of experience‐dependent neuronal plasticity. Anatomic magnetic resonance imaging (MRI) and psychophysical vision testing was carried out on 74 subjects divided into two age ranges, 7–12 years and 18–35 years, and three diagnoses, strabismic amblyopia, anisometropic amblyopia, and normal vision. We report a behavioral impairment in contrast sensitivity for subjects with amblyopia, consistent with previous reports. When the high‐resolution MRI brain images were analyzed quantitatively with optimized voxel‐based morphometry, results indicated that adults and children with amblyopia have decreased gray matter volume in visual cortical regions, including the calcarine sulcus, known to contain primary visual cortex. This finding was confirmed with a separate region‐of‐interest analysis. For the children with amblyopia, additional gray matter reductions in parietal‐occipital areas and ventral temporal cortex were detected, consistent with recent reports that amblyopia can result in spatial location and object processing deficits. These data are the first to provide possible neuroanatomic bases for the loss of binocularity and visual sensitivity in children and adults with amblyopia. Hum Brain Mapp 25:222–236, 2005. © 2005 Wiley‐Liss, Inc.

Many measures of visual function reach adult levels by about age 5, but some visual abilities continue to develop throughout adolescence. Little is known about the underlying functional anatomy of visual cortex in human infants or children. We used fMRI to measure the retinotopic organization of visual cortex in 15 children aged 7-12 years. Overall, we obtained adult-like patterns for most children tested. We found that significant head motion accounted for poor quality maps in a few tested children who were excluded from further analysis. When the maps from 10 children were compared with those obtained from 10 adults, the magnitude of retinotopic signals in visual areas V1, V2, V3, V3A, VP, and V4v was essentially the same between children and adults. Furthermore, one measure of intra-area organization, the cortical magnification function, did not significantly differ between adults and children for V1 or V2. However, quantitative analysis of visual area size revealed some significant differences beyond V1. Adults had larger extrastriate areas (V2, V3, VP, and V4v), when measured absolutely or as a proportion of the entire cortical sheet. We found that the extent and laterality of retinotopic signals beyond these classically defined areas, in parietal and lateral occipital cortex, showed some differences between adults and children. These data serve as a useful reference for studies of higher cognitive function in pediatric populations and for studies of children with vision disorders, such as amblyopia.

Although glaucoma treatments alter aqueous humor (AH) dynamics to lower intraocular pressure, the regulatory mechanisms of AH circulation and their contributions to the pathogenesis of ocular hypertension and glaucoma remain unclear. We hypothesized that gadolinium-enhanced magnetic resonance imaging (Gd-MRI) can visualize and assess AH dynamics upon sustained intraocular pressure elevation and pharmacologic interventions.Gadolinium contrast agent was systemically administered to adult rats to mimic soluble AH components entering the anterior chamber (AC) via blood-aqueous barrier. Dynamic Gd-MRI was applied to examine the signal enhancement in AC and vitreous body upon microbead-induced ocular hypertension and unilateral topical applications of latanoprost, timolol maleate, and brimonidine tartrate to healthy eyes.Gadolinium signal time courses in microbead-induced hypertensive eyes possessed faster initial gadolinium uptake and higher peak signals in AC than control eyes, reflective of reduced gadolinium clearance upon microbead occlusion. Opposite trends were observed in latanoprost- and timolol-treated eyes, indicative of their respective drug actions on increased uveoscleral outflow and reduced AH production. The slowest initial gadolinium uptake but strongest peak signals were found in AC of both brimonidine-treated and untreated fellow eyes. These findings drew attention to the systemic effects of topical hypotensive drug treatment. Gadolinium leaked into the vitreous of microbead-induced hypertensive eyes and brimonidine-treated and untreated fellow eyes, suggestive of a compromise of aqueous-vitreous or blood-ocular barrier integrity.Gadolinium-enhanced MRI allows spatiotemporal and quantitative evaluation of altered AH dynamics and ocular tissue permeability for better understanding the physiological mechanisms of ocular hypertension and the efficacy of antiglaucoma drug treatments.

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.