MAIA microperimeter for short-duration fixation stability measurements in central vision loss: Repeatability and comparison with the Nidek MP1.

PURPOSE: This study reports the repeatability of 20 s-duration fixation stability measurements recorded with the Macular Integrity Assessment (MAIA) microperimeter in patients with central vision loss, in contrast to the Nidek MP1 microperimeter. METHODS: Fixation stability was recorded in 39 eyes of 25 patients with macular disease using MAIA and the MP1 for 20 s intervals, twice for each eye, with each instrument. Twenty eyes were identified as the better eye (BE) and 19 eyes as the worse eye (WE). Fixation stability was quantified with the 95% bivariate contour ellipse area (BCEA), logarithmically transformed. Bland-Altman plots were used to determine the 95% limits of agreement. RESULTS: For MAIA, the 95% limits of agreement were ±0.84 log deg2 for the BE and ±0.66 log deg2 for the WE. Similarly, for the MP1 these limits were ±0.48 log deg2 for the BE and ±0.72 log deg2 for the WE. Inter-device repeatability was modest, ±1.09 log deg2 for the BE and ±1.01 log deg2 for the WE, and a proportional bias was detected. Occasionally, MAIA did not register all the expected number of data points, and included far outliers in the BCEA calculation; the inter-device repeatability did not improve when these outliers were removed. CONCLUSIONS: Repeatability of 20 s-duration fixation stability examination in patients with central vision loss is specific to the instrument used. We recommend that only data from same type of microperimeter with the same fixation duration should be compared when using fixation stability as an outcome measure to monitor disease progression, effect of treatment or in clinical trials.

A DOUBLE-MASKED, RANDOMIZED, SHAM-CONTROLLED, SINGLE-CENTER STUDY WITH PHOTOBIOMODULATION FOR THE TREATMENT OF DRY AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The LIGHTSITE I study investigated the efficacy and safety of photobiomodulation (PBM) treatment in subjects with dry age-related macular degeneration. METHODS: Thirty subjects (46 eyes) were treated with the Valeda Light Delivery System, wherein subjects underwent two series of treatments (3× per week for 3-4 weeks) over 1 year. Outcome measures included best-corrected visual acuity, contrast sensitivity, microperimetry, central drusen volume and drusen thickness, and quality of life assessments. RESULTS: Photobiomodulation-treated subjects showed a best-corrected visual acuity mean letter score gain of 4 letters immediately after each treatment series at Month 1 (M1) and Month 7 (M7). Approximately 50% of PBM-treated subjects showed improvement of ≥5 letters versus 13.6% in sham-treated subjects at M1. High responding subjects (≥5-letter improvement) in the PBM-treated group showed a gain of 8 letters after initial treatment (P < 0.01) and exhibited earlier stages of age-related macular degeneration disease. Statistically significant improvements in contrast sensitivity, central drusen volume, central drusen thickness, and quality of life were observed (P < 0.05). No device-related adverse events were reported. CONCLUSION: Photobiomodulation treatment statistically improved clinical and anatomical outcomes with more robust benefits observed in subjects with earlier stages of dry age-related macular degeneration. Repeated PBM treatments are necessary to maintain benefits. These pilot findings support previous reports and suggest the utility of PBM as a safe and effective therapy in subjects with dry age-related macular degeneration.

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

PURPOSE: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. METHODS: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. RESULTS: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. CONCLUSION: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.

Reading with central vision loss: binocular summation and inhibition.

PURPOSE: There are conflicting reports as to whether there is a binocular advantage or disadvantage when reading with central vision loss. This study examined binocular reading summation in patients with macular degeneration. METHODS: Seventy-one patients with bilateral central vision loss [mean age: 63 (S.D. = 21) years] participated. Reading performances during binocular and monocular viewing with the better eye (i.e., the eye with the best monocular visual acuity) were evaluated using different versions of the Italian MNREAD reading chart (www.precision-vision.com). Fixation stability and preferred retinal loci (PRLs) were recorded monocularly for each eye. The overall sample was split into inhibition, equality, and summation groups based on the binocular ratio (i.e., binocular/monocular) of the maximum reading speed. RESULTS: 41% of patients experienced binocular inhibition, 42% summation, and 17% equality. Binocular reading speed of the inhibition group was approximately 30 words per minute slower than those of the equality and summation groups, although the inhibition group had the best visual acuity. These patients generally had monocular PRLs in non-corresponding locations temporal or nasal to the scotoma, had the largest interocular acuity difference and lacked residual stereopsis. The three groups did not differ in fixational control, contrast sensitivity or critical print size. CONCLUSIONS: Equal proportions of patients with central vision loss show binocular reading summation and inhibition. Patients with binocular reading inhibition have poorer reading performance and different clinical characteristics than those with binocular reading summation and equality.

RETINAL DETACHMENT AND RETROBULBAR CYSTS IN A LARGE COHORT OF OPTIC NERVE COLOBOMA.

PURPOSE: To examine the relationship between retinal detachment and retrobulbar cysts in patients with optic nerve coloboma (ONC) and Morning Glory syndrome (MGS). METHODS: Patients diagnosed with either ONC or MGS were identified through a search of the Sick Kids database. Seventy-one patients either agreed to come in for a B-scan or had an incidental orbital B-scan or magnetic resonance imaging or both. Eyes with orbital B-scan ultrasound and/or magnetic resonance imaging images were assessed independently by two ophthalmologists and a radiologist for the presence of retrobulbar cysts. Retinal detachment was identified clinically with either indirect ophthalmoscopy or from fundus photographs. RESULTS: Forty-five of 71 (63%) and 26/71 (37%) patients had ONC and MGS, respectively. Retinal detachment occurred significantly more often in eyes with MGS than with ONC (9/17 [53%] vs. 5/45 [11%], P = 0.03, respectively). Retrobulbar cysts were not detected more often in MGS than in ONC (11/45 [24%] vs. 7/26 [27%]; P = 1.0). Eyes with retrobulbar cysts were significantly more likely to be associated with retinal detachment than those without (7/18 [39%] vs. 7/53 [13%]; P = 0.04). CONCLUSION: Retinal detachment occurs more frequently in MGS than in ONC in a cohort of patients referred to a specialist children's retinal service. Eyes with retrobulbar cysts are more likely to be associated with retinal detachment.

Worldwide Argus II implantation: recommendations to optimize patient outcomes.

BACKGROUND: A position paper based on the collective experiences of Argus II Retinal Prosthesis System investigators to review strategies to optimize outcomes in patients with retinitis pigmentosa undergoing retinal prosthesis implantation. METHODS: Retinal surgeons, device programmers, and rehabilitation specialists from Europe, Canada, Middle East, and the United States were convened to the first international Argus II Investigator Meeting held in Ann Arbor, MI in March 2015. The recommendations from the collective experiences were collected. Factors associated with successful outcomes were determined. RESULTS: Factors leading to successful outcomes begin with appropriate patient selection, expectation counseling, and preoperative retinal assessment. Challenges to surgical implantation include presence of staphyloma and inadequate Tenon's capsule or conjunctiva. Modified surgical technique may reduce risks of complications such as hypotony and conjunctival erosion. Rehabilitation efforts and correlation with validated outcome measures following implantation are critical. CONCLUSIONS: Bringing together Argus II investigators allowed the identification of strategies to optimize patient outcomes. Establishing an on-line collaborative network will foster coordinated research efforts to advance outcome assessment and rehabilitation strategies.

Bilateral Panuveitis Associated with Morvan Syndrome: A Case Report and Review of the Literature.

PURPOSE: Morvan syndrome (MoS) is a neurologic disorder belonging to a spectrum of autoimmune encephalitis, Contactin-associated protein-like 2 (Caspr2) antibody syndrome. We report a case of bilateral panuveitis associated with MoS. METHODS: Case report and review of the literature. RESULTS: A 57-year-old male with Morvan syndrome presented with painless vision loss and floaters. Initial visual acuities were 20/50 and 20/60. Hallmarks of this uveitis included persistently active vitritis, and nonhemorrhagic retinitis with nonperfusion and neovascularization. Uveitis consistently flared with attempted immunosuppressive tapers. Vision deteriorated to count fingers (2 ft) OU over 2.5 years despite corticosteroids, mycophenolate mofetil, intravenous immunoglobulin, adalimumab, and rituximab. Explanations for reduced final visual acuity included macular atrophy, disruption of retinal architecture, epiretinal membrane, vitritis, and cataract. CONCLUSIONS: This case constitutes the first report of uveitis associated with MoS and Caspr2 antibody syndrome, raising the question of autoimmunity targeting the retinal inner and/or outer plexiform layers.

Incidence of endophthalmitis and use of antibiotic prophylaxis after intravitreal injections.

PURPOSE: To report the incidence of endophthalmitis in association with different antibiotic prophylaxis strategies after intravitreal injections of anti-vascular endothelial growth factors and triamcinolone acetonide. DESIGN: Retrospective, comparative case series. PARTICIPANTS: Fifteen thousand eight hundred ninety-five intravitreal injections (9453 ranibizumab, 5386 bevacizumab, 935 triamcinolone acetonide, 121 pegaptanib sodium) were reviewed for 2465 patients between January 5, 2005, and August 31, 2010. The number of injections was determined from billing code and patient records. METHODS: The indications for injection included age-related macular degeneration, diabetic macular edema, central and branch retinal vein occlusion, and miscellaneous causes. Three strategies of topical antibiotic prophylaxis were used by the respective surgeons: (1) antibiotics given for 5 days after each injection, (2) antibiotics given immediately after each injection, and (3) no antibiotics given. MAIN OUTCOME MEASURES: The primary outcome measures were the incidence of culture-positive endophthalmitis and culture-negative cases of suspected endophthalmitis. RESULTS: Nine eyes of 9 patients with suspected endophthalmitis after injection were identified. Three of the 9 cases had culture-positive results. The overall incidence of endophthalmitis was 9 in 15 895. The incidence of culture-negative cases of suspected endophthalmitis and culture-proven endophthalmitis after injection was 6 in 15 895 and 3 in 15 895, respectively. Taking into account both culture-positive endophthalmitis and culture-negative cases of suspected endophthalmitis, the incidence per injection was 5 in 8259 for patients who were given antibiotics for 5 days after injection, 2 in 2370 for those who received antibiotics immediately after each injection, and 2 in 5266 who received no antibiotics. However, if considering culture-proven endophthalmitis alone, the use of topical antibiotics, given immediately or for 5 days after injection, showed lower rates of endophthalmitis compared with those without postinjection antibiotics. The risk of endophthalmitis after intravitreal injection varied among agents that were used. Among the 9 cases of clinically suspected endophthalmitis, regardless of prophylactic strategies used, the incidence of endophthalmitis per injection was 2 in 935 for triamcinolone acetonide, 3 in 9453 for ranibizumab, and 4 in 5386 for bevacizumab. CONCLUSIONS: The overall rate of intravitreal injection-related endophthalmitis is greater with the use of topical antibiotics, given immediately or for 5 days after the injection, compared with no antibiotics.

Retinal arteriolar hemodynamic response to a combined isocapnic hyperoxia and glucose provocation in early sight-threatening diabetic retinopathy.

PURPOSE: To quantify the magnitude of change of retinal arteriolar hemodynamics induced by a combined isocapnic hyperoxia and glucose provocation in diabetic patients with early sight-threatening diabetic retinopathy (DR) and in age-matched control subjects and to compare the response to that of an isocapnic hyperoxia provocation alone. The study hypothesis was that hyperglycemia reduces the retinal vascular reactivity response to a hyperoxic stimulus. METHODS: The sample comprised 17 control subjects (group 1), 15 patients with no clinically visible DR (group 2), 16 patients with mild-to-moderate nonproliferative DR (group 3), and 15 patients with diabetic macular edema (group 4). Retinal hemodynamic measurements were acquired in the subjects, at baseline and 1 hour after consuming a standardized oral glucose load drink while breathing oxygen isocapnic with baseline. RESULTS: Retinal blood velocity and flow significantly decreased in all groups (P < or = 0.001 and P < or = 0.0002, respectively) in response to a combined isocapnic hyperoxia and glucose provocation. The maximum-to-minimum velocity ratio significantly increased (P < or = 0.005), and wall shear rate (WSR) significantly decreased (P < or = 0.0002), in groups 1, 2, and 3, but not in group 4. The vascular reactivity response was not significantly different across the groups. The control group demonstrated a reduced change in flow (P = 0.009) and WSR (P = 0.010) to the combined isocapnic hyperoxia and glucose provocation compared with that of hyperoxia alone. CONCLUSIONS: The vascular reactivity response to a combined isocapnic hyperoxia and glucose provocation produced a pronounced reduction in blood flow. Unlike the response to hyperoxia alone, the vascular reactivity response was not significantly different across the groups. Hyperglycemia reduced the retinal vascular reactivity response to hyperoxia in age-matched control subjects.

Rehabilitation of lost functional vision with the Argus II retinal prosthesis.

The Argus II retinal prosthesis is the first commercially available device for restoration of vision in patients with Retinitis Pigmentosa or with similar retinal pathology who still have minimal residual native vision. The technology is able to restore vision with production of artificial visual percepts which usually are given adequate useful interpretation by the visual system in most implanted patients. The technology usually produces visual perception at the level of shape identification or better in some cases enabling in many less dependence on vision substitution devices and skills. There is no consensus among vision rehabilitation practitioners on single methods for assessments, outcome measures and training, yet there is constant progress in these areas of concern. Hence the current vision rehabilitation practice related to the implantation of the Argus II retinal prosthesis is a work in progress with many learning opportunities for all involved. All agree that implementation of this technology in clinical practice requires the combined work of a multi-disciplinary team which includes a specialized surgical team as well as a specialized rehabilitation team in order to obtain optimal results. Our own experience is presented in this paper and indicates so far that the Argus II technology is beneficial to patients and that it could be successfully managed within the Canadian heath care system.

The Toronto experience with the Argus II retinal prosthesis: new technology, new hope for patients.

Surgical restoration of vision with retinal prostheses is a new and developing technology currently available in a select group of countries, Canada among them. The Argus II retinal prosthesis is the first commercially available device for restoration of vision in patients with Retinitis Pigmentosa or with similar retinal pathology who still have minimal residual native vision. The surgery is complex and requires training however it is within the abilities of any experienced retina surgeon. Surgical experience builds up with each case and in our patients length of surgery constantly went down. Complications occurred however we experienced no catastrophic events. Most notable is that in our implanted cases the Argus II technology proved to be beneficial to most patients. In order to obtain optimal results with this surgical intervention it is absolutely required that the surgical work is complemented simultaneously with the work of a specialized rehabilitation team. A review of the technology, of our experience, comments and concerns is presented in this paper.

Retinal hemodynamics in early diabetic macular edema.

The objective of this study was to establish the baseline retinal hemodynamic characteristics of stratified groups of diabetic patients at increasing risk for the development of diabetic macular edema (DME). Group 1 had 50 control subjects, group 2 had 56 diabetic patients without clinically visible retinopathy, group 3 had 54 diabetic patients with microaneurysms and/or hard exudates within two disc diameters of the fovea in the absence of clinically manifest DME, and group 4 had 40 patients with clinically manifest DME. Retinal hemodynamics (diameter, velocity, maximum-to-minimum velocity ratio, and flow) were assessed. Intraocular pressure, blood pressure, and relevant systemic markers of diabetes control and complications were also undertaken. The maximum-to-minimum velocity ratio was elevated with increasing risk of clinically significant DME (P < 0.0001). No significant differences were found between the groups with respect to diameter, velocity, or flow. The maximum-to-minimum velocity ratio was correlated to age, duration of diabetes, blood pressure, pulse rate, intraocular pressure, and serum potassium levels. In conclusion, the maximum-to-minimum velocity ratio was significantly increased with increasing risk of development of DME. Retinal arteriolar hemodynamics were positively correlated to age, duration of diabetes, and blood pressure. These findings suggest a reduction in the compliance (i.e., an increase of vascular rigidity) of the arteriolar circulation with increasing risk of DME.

Retinal arteriolar diameter, blood velocity, and blood flow response to an isocapnic hyperoxic provocation in early sight-threatening diabetic retinopathy.

PURPOSE: To quantify the magnitude of retinal arteriolar vascular reactivity in diabetic patients stratified by severity of retinopathy and in age-matched control subjects. The sample comprised 21 nondiabetic control subjects (group 1), 19 patients with no clinically visible DR (group 2), 19 patients with mild-to-moderate nonproliferative DR and without clinically evident diabetic macular edema (DME) (group 3), and 17 patients with DME (group 4). methods Subjects initially breathed air, followed by oxygen, while isocapnia was maintained. Retinal arteriolar diameter and blood velocity measurements were acquired simultaneously. RESULTS: Changes in blood velocity and wall shear rate (WSR) were significantly less in groups 3 and 4 (P < 0.0001 and P = 0.0002, respectively) than in groups 1 and 2. Change in blood flow was significantly less in group 4 (P < 0.004) than in groups 1 and 2. The change in maximum-to-minimum (max:min) ratio was significantly less in groups 2 and 4 than in group 1 (P = 0.001). There was a significant relationship between baseline objective edema indices and vascular reactivity. The magnitude of vascular reactivity in response to isocapnic hyperoxia was reduced in those individuals with clinically evident DR relative to subjects without diabetes. CONCLUSIONS: The differences in vascular reactivity occurred in the absence of any difference in baseline hemodynamic values. Vascular reactivity is impaired in early sight-threatening DR, and this impairment is related to the objectively defined magnitude of retinal edema.

Photobiomodulation reduces drusen volume and improves visual acuity and contrast sensitivity in dry age-related macular degeneration.

PURPOSE: To evaluate the efficacy of photobiomodulation (PBM) treatment for patients with dry age-related macular degeneration (AMD). METHODS: Assessments on 42 eyes with dry AMD (age related eye disease study (AREDS) 2-4) were conducted. Multiwavelength light emitting diode (LED) light comprising of yellow (590 nm), red (670 nm) and near-infrared (790 nm) bandwidths was applied to subjects' eyes for a treatment course of 3 weeks. Outcome measures were changes in best-corrected visual acuity (BCVA), contrast sensitivity (CS), drusen volume and central drusen thickness. RESULTS: Significant improvement in mean BCVA of 5.90 letters (p < 0.001) was seen on completion of the 3-week treatment and 5.14 letters (p < 0.001) after 3 months. Contrast sensitivity improved significantly (log unit improvement of 0.11 (p = 0.02) at 3 weeks and 3 months (log unit improvement of 0.16 (p = 0.02) at three cycles per degree. Drusen volume decreased by 0.024 mm3 (p < 0.001) and central drusen thickness was significantly reduced by a mean of 3.78 µm (p < 0.001), while overall central retinal thickness and retinal volume remained stable. CONCLUSION: This is the first study demonstrating improvements in functional and anatomical outcomes in dry AMD subjects with PBM therapy. These findings corroborate an earlier pilot study that looked at functional outcome measures. The addition of anatomical evidence contributes to the basis for further development of a non-invasive PBM treatment for dry AMD.

Pain Associated With a Subconjunctival Cefazolin-Lidocaine Mixture in Retinal Surgery:A Randomized Control Trial.

BACKGROUND AND OBJECTIVE: The purpose of this randomized, single-masked clinical trial is to explore whether cefazolin mixed with 2% lidocaine can reduce pain. PATIENTS AND METHODS: Patients naïve to ophthalmic surgery were randomized to subconjunctival injection of either a 0.5 mL cefazolin-balanced salt solution (0.3 mL cefazolin and 0.2 mL balanced salt solution) or 0.5 mL cefazolin-lidocaine solution (0.3 mL cefazolin and 0.2 mL 2% lidocaine) during retinal surgery with a retrobulbar block. Pain scores were obtained at the start of surgery, middle of surgery, before and after cefazolin administration, and postoperatively. RESULTS: A total of 54 patients were recruited; 44.6% were male, and the mean age was 60.1 years ± 13.5 years. There were no statistically significant differences between the groups' operative characteristics or pain scores at each study time point. CONCLUSION: In pars plana vitrectomy with or without phacoemulsification and intraocular lens insertion, subconjunctival cefazolin mixed with lidocaine conferred no added analgesic benefit. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:881-886.].

Age-related macular degeneration: is polypoidal choroidal vasculopathy recognized and treated?

OBJECTIVE: To assess how polypoidal choroidal vasculopathy (PCV) is recognized and treated, and to assess whether treatment outcomes are different between Chinese and Caucasian Canadian patients with age-related macular degeneration (AMD). DESIGN: Retrospective chart review. PARTICIPANTS: 154 eyes from 135 Chinese patients and 2291 eyes from 1792 Caucasian patients who were newly diagnosed with either AMD or PCV and had more than 1 year of follow-up were included. METHODS: All newly diagnosed AMD patients presenting to the Retina Service of 3 Toronto University Hospitals, between March 25, 2008, to September 30, 2014, were reviewed. RESULTS: 10/154 eyes (6.5%) in Chinese Canadians and 16/2291 eyes (0.7%) in Caucasian Canadians were diagnosed as having PCV. Indocyanine green angiography (ICGA) was used to diagnose PCV in 20% of Chinese Canadians and 8.8% of Caucasian Canadians. Clinical practices with a larger percentage of Chinese patients were more likely to diagnose PCV in both Chinese (p = 0.004) and Caucasian patients (p = 0.03), were more likely to use photodynamic therapy (PDT) (p < 0.01), and had significantly greater central retinal thickness decrease (p < 0.001). CONCLUSION: Our study has shown that PCV is under-recognized in a Canadian population, and ICGA is underutilized. In clinical practices with a greater portion of Chinese patients, PCV is more often recognized and PDT is used more liberally.

Agreement of the Heidelberg Retina Tomograph II macula edema module with fundus biomicroscopy in diabetic maculopathy.

OBJECTIVES: To estimate the agreement between the macular edema maps (MEMs) of the Retina Module of the Heidelberg Retina Tomograph II (Heidelberg Engineering, Heidelberg, Germany) and contact lens fundus biomicroscopy (FB) and to assess the influence of combining MEM data with the results of short-wavelength automated perimetry (SWAP) and fluorescein angiography (FA) on diagnostic test performance. DESIGN: Prospective, observational case series. METHODS: Twenty patients (20 eyes) with diabetic retinopathy with or without clinically manifest macular edema (11 and 9 eyes, respectively) were enrolled. All patients underwent full ophthalmologic examination and also MEM assessment, SWAP, and FA. RESULTS: Using FB as the "gold standard," the agreement between the MEMs and FB was very good (Kendall coefficient of concordance, 0.80). Macular edema maps showed good agreement with FA and SWAP (Kendall coefficient, 0.64 and 0.65). Virtually all of the edematous areas detected with MEM but not seen clinically had decreased sensitivity on SWAP and/or fluorescein leakage. CONCLUSIONS: Macular edema maps demonstrated very good agreement with FB. Combining the results of FA and SWAP with those of the MEMs provided supporting evidence of concomitant blood-retinal barrier leakage and visual dysfunction, respectively, in areas of early retinal thickening. Prospective studies are ongoing to fully assess the diagnostic test performance of MEMs in the detection of early and progressive diabetic macular edema.