Phase 3 Randomized Clinical Trial of the Safety and Efficacy of Travoprost Intraocular Implant in Patients with Open-Angle Glaucoma or Ocular Hypertension.

PURPOSE: To evaluate the safety and intraocular pressure (IOP)-lowering efficacy of 2 models of the travoprost intraocular implant (fast-eluting [FE] and slow-eluting [SE] types) from 1 of 2 phase 3 trials (the GC-010 trial). DESIGN: Multicenter, randomized, double-masked, sham-controlled, noninferiority trial. PARTICIPANTS: Patients with open-angle glaucoma or ocular hypertension having an unmedicated baseline mean diurnal IOP (average of 8 am, 10 am, and 4 pm time points) of ≥ 21 mmHg, and IOP of ≤ 36 mmHg at each of the 8 am, 10 am, and 4 pm timepoints at baseline. METHODS: Study eyes were randomized to the travoprost intraocular implant (FE implant [n = 200] or SE implant [n = 197] model) or to timolol ophthalmic solution 0.5% twice daily (n = 193). MAIN OUTCOME MEASURES: The primary outcome was mean change from baseline IOP in the study eye at 8 am and 10 am, at each of day 10, week 6, and month 3. Safety outcomes included adverse events (AEs) and ophthalmic assessments. RESULTS: Mean IOP reduction from baseline over the 6 time points ranged from 6.6 to 8.4 mmHg for the FE implant group, from 6.6 to 8.5 mmHg for the SE implant group, and from 6.5 to 7.7 mmHg for the timolol group. The primary efficacy end point was met; the upper limit of the 95% confidence interval of the difference between the implant groups and the timolol group was < 1 mmHg at all 6 time points. Study eye AEs, most of mild or moderate severity, were reported in 21.5%, 27.2%, and 10.8% of patients in the FE implant, SE implant, and timolol groups, respectively. The most common AEs included iritis (FE implant, 0.5%; SE implant, 5.1%), ocular hyperemia (FE implant, 3.0%; SE implant, 2.6%), reduced visual acuity (FE implant, 1.0%; SE implant, 4.1%; timolol, 0.5%), and IOP increased (FE implant, 3.5%; SE implant, 2.6%; timolol, 2.1%). One serious study eye AE occurred (endophthalmitis). CONCLUSIONS: The travoprost intraocular implant demonstrated robust IOP reduction over the 3-month primary efficacy evaluation period after a single administration. The IOP-lowering efficacy in both implant groups was statistically and clinically noninferior to that in the timolol group, with a favorable safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A Randomized Trial to Improve Adherence to Follow-up Eye Examinations Among People With Glaucoma.

INTRODUCTION: Appointment nonadherence is common among people with glaucoma, making it difficult for eye care providers to monitor glaucoma progression. Our objective was to determine whether the use of patient navigators, in conjunction with social worker support, could increase adherence to recommended follow-up eye appointments. METHODS: A randomized, controlled trial evaluated the effectiveness of an intervention that used patient navigators and social workers to improve patient adherence to follow-up eye care compared with usual care. Participants with glaucoma and other eye diseases (N = 344) were identified at primary care clinics in community settings through telemedicine screening of imaging and then randomized to enhanced intervention (EI) or usual care (UC). Data on participants' visits with local ophthalmologists were collected for up to 3 years from randomization. Groups were compared for timely attendance at the first visit with the local ophthalmologist and adherence to recommended follow-up visits. RESULTS: Timely attendance at the first visit was higher for EI than UC (74.4% vs 39.0%; average relative risk [aRR] = 1.85; 95% CI, 1.51-2.28; P < .001). Rates of adherence to recommended annual follow-up during year 1 were 18.6% in the EI group and 8.1% in the usual care group (aRR = 2.08; 95% CI, 1.14-3.76; P = .02). The aRR across years 2 and 3 was 3.92 (95% CI, 1.24-12.43; P = .02). CONCLUSION: An intervention using patient navigators and social workers doubled the rate of adherence to annual recommended follow-up eye care compared with usual care in community settings, and was effective at increasing connections with local ophthalmologists. Interventions to further improve long-term adherence are needed.

iStent inject trabecular micro-bypass stents with topical prostaglandin as standalone treatment for open-angle glaucoma: 4-year outcomes.

IMPORTANCE: Long-term data are needed regarding effective and safe glaucoma treatment modalities. BACKGROUND: This study evaluated 4-year outcomes of second-generation trabecular micro-bypass stent implantation (iStent inject) combined with topical travoprost in open-angle glaucoma (OAG). DESIGN: Prospective, non-randomized, multi-surgeon study at a tertiary care ophthalmology centre. PARTICIPANTS: OAG subjects with preoperative intraocular pressure (IOP) 18 to 30 mmHg on two medications and 22 to 38 mmHg post-washout. METHODS: Subjects (n = 53) underwent standalone iStent inject implantation and started travoprost on postoperative Day 1. Measures included IOP, medications, comprehensive ophthalmic examinations and testing, and adverse events (AEs). Annual medication washouts were performed. MAIN OUTCOME MEASURES: Mean medicated and unmedicated IOP; and proportions of eyes with IOP ≤18mmHg, ≤15 mmHg, or ≥20% reduced while on travoprost vs screening IOP on two medications. RESULTS: At 48 months postoperative, 85% of eyes reduced IOP ≥20% on travoprost vs screening IOP on 2 medications; 92% of eyes had IOP ≤18 mmHg on travoprost; and 83% had IOP ≤15 mmHg on travoprost. At Month 49 (post-washout), 90% of eyes reduced IOP ≥20% vs preoperative washout IOP. Throughout follow-up, mean IOP on travoprost was 11.9 to 13.0 mmHg (34%-40% reduced vs 19.7 mmHg on 2 medications preoperatively; P < .0001 throughout), and post-washout IOP was 16.5 to 17.7 mmHg (28%-34% reduced vs 24.9 mmHg preoperatively; P < .0001 throughout). Favourable safety included minimal AEs; stable visual acuity, cup-to-disc ratio and visual fields; and no secondary surgeries. CONCLUSIONS AND RELEVANCE: Combining iStent inject implantation with topical prostaglandin produced significant and safe 4-year IOP and medication reductions in OAG.

Philadelphia Telemedicine Glaucoma Detection and Follow-Up Study: Cataract Classifications Following Eye Screening.

Background:Cataracts are a major cause of visual impairment and blindness in the United States and worldwide.Introduction:Risk factors for cataracts include age over 40 years, smoking, diabetes, low socioeconomic status, female sex, steroid use, ocular trauma, genetic factors, and exposure to ultraviolet-B light. Community-based telemedicine vision screenings can be an efficient method for detecting cataracts in underserved populations. The Philadelphia Telemedicine Glaucoma Detection and Follow-Up Study reports the prevalence and risk factors for cataracts in individuals screened and examined for glaucoma and other eye diseases.Materials and Methods:A total of 906 high-risk individuals were screened for glaucoma using telemedicine in seven primary care practices and four Federally Qualified Health Centers in Philadelphia. Participants with suspicious nerves or other abnormalities on fundus photographs, unreadable images, and ocular hypertension returned for an eye examination with an ophthalmologist at the same community location.Results:Of the participants screened through telemedicine, 347 (38.3%) completed a follow-up eye examination by an ophthalmologist. Of these, 267 (76.9%) were diagnosed with cataracts, of which 38 (14.2%) had visually significant cataracts. Participants who were diagnosed with visually significant cataract were more likely to be older (p < 0.001), have diabetes (p = 0.003), and worse visual acuity (p < 0.001).Discussion:Our study successfully detected and confirmed cataracts in a targeted, underserved urban population at high risk for eye disease.Conclusions:Telemedicine programs offer an opportunity to identify and refer individuals who would benefit from continuous follow-up eye care and treatment to improve visual function and quality of life.

Mutations of conserved non-coding elements of PITX2 in patients with ocular dysgenesis and developmental glaucoma.

Mutations in FOXC1 and PITX2 constitute the most common causes of ocular anterior segment dysgenesis (ASD), and confer a high risk for secondary glaucoma. The genetic causes underlying ASD in approximately half of patients remain unknown, despite many of them being screened by whole exome sequencing. Here, we performed whole genome sequencing on DNA from two affected individuals from a family with dominantly inherited ASD and glaucoma to identify a 748-kb deletion in a gene desert that contains conserved putative PITX2 regulatory elements. We used CRISPR/Cas9 to delete the orthologous region in zebrafish in order to test the pathogenicity of this structural variant. Deletion in zebrafish reduced pitx2 expression during development and resulted in shallow anterior chambers. We screened additional patients for copy number variation of the putative regulatory elements and found an overlapping deletion in a second family and in a potentially-ancestrally-related index patient with ASD and glaucoma. These data suggest that mutations affecting conserved non-coding elements of PITX2 may constitute an important class of mutations in patients with ASD for whom the molecular cause of their disease have not yet been identified. Improved functional annotation of the human genome and transition to sequencing of patient genomes instead of exomes will be required before the magnitude of this class of mutations is fully understood.

Prospective, Randomized, Controlled Pivotal Trial of an Ab Interno Implanted Trabecular Micro-Bypass in Primary Open-Angle Glaucoma and Cataract: Two-Year Results.

PURPOSE: Evaluate the safety and effectiveness of an ab interno implanted (iStent inject) Trabecular Micro-Bypass System (Glaukos Corporation, San Clemente, CA) in combination with cataract surgery in subjects with mild to moderate primary open-angle glaucoma (POAG). DESIGN: Prospective, randomized, single-masked, concurrently controlled, multicenter clinical trial. PARTICIPANTS: Eyes with mild to moderate POAG and preoperative intraocular pressure (IOP) ≤24 mmHg on 1 to 3 medications, unmedicated diurnal IOP (DIOP) 21 to 36 mmHg, and cataract requiring surgery. METHODS: After uncomplicated cataract surgery, eyes were randomized 3:1 intraoperatively to ab interno implantation of iStent inject (Model G2-M-IS; treatment group, n = 387) or no stent implantation (control group, n = 118). Subjects were followed through 2 years postoperatively. Annual washout of ocular hypotensive medication was performed. MAIN OUTCOME MEASURES: Effectiveness end points were ≥20% reduction from baseline in month 24 unmedicated DIOP and change in unmedicated month 24 DIOP from baseline. Safety measures included best spectacle-corrected visual acuity (BSCVA), slit-lamp and fundus examinations, gonioscopy, pachymetry, specular microscopy, visual fields, complications, and adverse events. RESULTS: The groups were well balanced preoperatively, including medicated IOP (17.5 mmHg in both groups) and unmedicated DIOP (24.8±3.3 mmHg vs. 24.5±3.1 mmHg in the treatment and control groups, respectively, P = 0.33). At 24 months, 75.8% of treatment eyes versus 61.9% of control eyes experienced ≥20% reduction from baseline in unmedicated DIOP (P = 0.005), and mean reduction in unmedicated DIOP from baseline was greater in treatment eyes (7.0±4.0 mmHg) than in control eyes (5.4±3.7 mmHg; P < 0.001). Of the responders, 84% of treatment eyes and 67% of control eyes were not receiving ocular hypotensive medication at 23 months. Furthermore, 63.2% of treatment eyes versus 50.0% of control eyes had month 24 medication-free DIOP ≤18 mmHg (difference 13.2%; 95% confidence interval, 2.9-23.4). The overall safety profile of the treatment group was favorable and similar to that in the control group throughout the 2-year follow-up. CONCLUSIONS: Clinically and statistically greater reductions in IOP without medication were achieved after iStent inject implantation with cataract surgery versus cataract surgery alone, with excellent safety through 2 years.

Is primary open-angle glaucoma an ocular manifestation of systemic disease?

Primary open-angle glaucoma is currently characterized by a pattern of progressive retinal ganglion cell loss that stems from a complex underlying pathophysiology that remains poorly elucidated. The roles of blood flow and intraocular pressure (IOP) in glaucoma pathogenesis have been extensively studied. Further, it has been established that lowering IOP can slow the progression of glaucoma. In addition, a number of influential factors have emerged and gained momentum over the years. Increasing evidence implicates the contributions of low cerebrospinal fluid pressure, autoimmunity, neurodegeneration, and impaired autoregulation towards glaucoma pathophysiology. We aggregate and explore these different camps of thought that have garnered attention over the last few decades, and, in doing so, aim to challenge the long-standing view of glaucoma as a primary disease of the eye. A shift in our perspective towards understanding glaucoma as an ocular manifestation of systemic dysregulation may lead ultimately to better clinical management of the disease.

Awareness of ocular diagnosis, transportation means, and barriers to ophthalmology follow-up in the Philadelphia Telemedicine Glaucoma Detection and Follow-up Study.

Purpose: The purpose of this study was to assess factors affecting follow-up eye care in participants enrolled in the Philadelphia Telemedicine Glaucoma Detection and Follow-up Study, such as awareness of ocular diagnosis, availability of transportation methods, and reasons for missing eye care appointments. Methods: The sample included 172 participants who were randomized to the intervention group and contacted by the social worker. Results: A total of 155 participants completed the assessment form, which was used as an instrument to assess factors affecting adherence to follow-up eye care. The main reasons for missing eye exam appointments were feeling ill (38.1%, n = 59) and forgetting the appointment (34.2%, n = 53). In addition, 45 (29.2%) participants were unaware of or did not comprehend the severity of their ocular diagnosis. Common methods of transportation included public transportation (31.6%, n = 49), driving (29.7%, n = 46), and being driven (27.7%, n = 43) to their appointment. Conclusion: These results suggest that individuals in need of eye care may benefit from additional assistance of a social worker regarding ongoing eye exam appointment reminders and in-depth explanation of their ocular diagnosis.

Validation of the structure-function correlation report from the heidelberg edge perimeter and spectral-domain optical coherence tomography.

PURPOSE: To compare the diagnostic assessment of glaucoma specialists with an automated structure-function correlation report combining visual field (VF) and spectral-domain optical coherence tomography (SD-OCT) imagining in subjects with glaucoma. METHODS: This prospective, cross-sectional study was conducted at Wills Eye Hospital, Philadelphia, PA, USA. Subjects with glaucoma received ophthalmic examination, VF testing, and SD-OCT imaging. An automated report was generated describing structure-function correlations between the two structural elements [retinal nerve fiber layer (RNFL) and Bruch's membrane opening-minimum rim width (MRW)] and VF sectors. Three glaucoma specialists masked to the automated report and to each other identified clinically significant structure-function correlations between the VF and SD-OCT reports. Raw agreement and chance-corrected agreement (kappa statistics) between the automated report and the clinical assessments were compared. RESULTS: A total of 53 eyes from 45 subjects with glaucoma were included in this study. The overall agreement between the automated report and clinical assessment comparing MRW and VF was good at 74.8% with a kappa of 0.62 (95% CI 0.55-0.69). Agreements for the six different MRW sections were moderate to good with kappa values ranging from 0.54 to 0.69. For mean RNFL thickness and VF comparisons, agreement between the automated report and clinical assessment was 75.4% with a kappa of 0.62 (95% CI 0.54-0.70). For different RNFL sectors, kappa values ranged from 0.47 (moderate agreement) to 0.80 (good agreement). CONCLUSIONS: This study suggests that the automated structure-function report combining results from the SD-OCT and the HEP may assist in the evaluation and management of glaucoma.

Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs.

Two decades after the discovery of the first animal microRNA (miRNA), the number of miRNAs in animal genomes remains a vexing question. Here, we report findings from analyzing 1,323 short RNA sequencing samples (RNA-seq) from 13 different human tissue types. Using stringent thresholding criteria, we identified 3,707 statistically significant novel mature miRNAs at a false discovery rate of ≤ 0.05 arising from 3,494 novel precursors; 91.5% of these novel miRNAs were identified independently in 10 or more of the processed samples. Analysis of these novel miRNAs revealed tissue-specific dependencies and a commensurate low Jaccard similarity index in intertissue comparisons. Of these novel miRNAs, 1,657 (45%) were identified in 43 datasets that were generated by cross-linking followed by Argonaute immunoprecipitation and sequencing (Ago CLIP-seq) and represented 3 of the 13 tissues, indicating that these miRNAs are active in the RNA interference pathway. Moreover, experimental investigation through stem-loop PCR of a random collection of newly discovered miRNAs in 12 cell lines representing 5 tissues confirmed their presence and tissue dependence. Among the newly identified miRNAs are many novel miRNA clusters, new members of known miRNA clusters, previously unreported products from uncharacterized arms of miRNA precursors, and previously unrecognized paralogues of functionally important miRNA families (e.g., miR-15/107). Examination of the sequence conservation across vertebrate and invertebrate organisms showed 56.7% of the newly discovered miRNAs to be human-specific whereas the majority (94.4%) are primate lineage-specific. Our findings suggest that the repertoire of human miRNAs is far more extensive than currently represented by public repositories and that there is a significant number of lineage- and/or tissue-specific miRNAs that are uncharacterized.

Steady-state pattern electroretinogram and short-duration transient visual evoked potentials in glaucomatous and healthy eyes.

IMPORTANCE: This study evaluates two rapid electrophysiological glaucoma diagnostic tests that may add a functional perspective to glaucoma diagnosis. BACKGROUND: This study aimed to determine the ability of two office-based electrophysiological diagnostic tests, steady-state pattern electroretinogram and short-duration transient visual evoked potentials, to discern between glaucomatous and healthy eyes. DESIGN: This is a cross-sectional study in a hospital setting. PARTICIPANTS: Forty-one patients with glaucoma and 41 healthy volunteers participated in the study. METHODS: Steady-state pattern electroretinogram and short-duration transient visual evoked potential testing was conducted in glaucomatous and healthy eyes. A 64-bar-size stimulus with both a low-contrast and high-contrast setting was used to compare steady-state pattern electroretinogram parameters in both groups. A low-contrast and high-contrast checkerboard stimulus was used to measure short-duration transient visual evoked potential parameters in both groups. MAIN OUTCOME MEASURES: Steady-state pattern electroretinogram parameters compared were MagnitudeD, MagnitudeD/Magnitude ratio, and the signal-to-noise ratio. Short-duration transient visual evoked potential parameters compared were amplitude and latency. RESULTS: MagnitudeD was significantly lower in glaucoma patients when using a low-contrast (P = 0.001) and high-contrast (P < 0.001) 64-bar-size steady-state pattern electroretinogram stimulus. MagnitudeD/Magnitude ratio and SNR were significantly lower in the glaucoma group when using a high-contrast 64-bar-size stimulus (P < 0.001 and P = 0.010, respectively). Short-duration transient visual evoked potential amplitude and latency were not significantly different between the two groups. CONCLUSIONS AND RELEVANCE: Steady-state pattern electroretinogram was effectively able to discern between glaucomatous and healthy eyes. Steady-state pattern electroretinogram may thus have a role as a clinically useful electrophysiological diagnostic tool.

The Effects of Latanoprost With Benzalkonium Chloride Versus Travoprost With SofZia on the Ocular Surface.

PURPOSE: To assess ocular surface changes in participants using latanoprost with benzalkonium chloride (Xalatan) and travoprost with SofZia (Travatan Z). METHODS: In this prospective, open-label, nonrandomized cohort study, participants were classified into two groups: group 1 (n=28) naive to glaucoma therapy, group 2 (n=27) on previous Xalatan monotherapy in both eyes. Both groups started (or continued) Xalatan in the right eye and Travatan Z in the left eye. Baseline, 1-, and 2-month measurements of tear breakup time (TBUT), corneal staining score, conjunctival staining score, conjunctival hyperemia score, tear production, and intraocular pressure were obtained. The Ocular Surface Disease Index questionnaire measured participants' comfort and dryness symptoms. Medication preference was recorded. RESULTS: Data were collected from 55 participants. Tear breakup time at baseline and 1-month follow-up in group 1 was significantly longer than that of group 2 (P=0.005). At 2 months, there was no significant difference in TBUT between the two groups (P=0.779). Tear production in group 1 at all three time points was significantly higher than group 2 (P<0.05). Conjunctival staining score at 2 months in group 1 was significantly higher than group 2 (P=0.031). There was no significant difference in other parameters between the groups at any other time point. No significant difference in any parameter was found between Xalatan and Travatan Z (intragroup comparison). CONCLUSIONS: Significant differences in ocular surface characteristics were detected between groups, but no significant difference was detected between participants treated with Xalatan and Travatan Z.

Implantation of two second-generation trabecular micro-bypass stents and topical travoprost in open-angle glaucoma not controlled on two preoperative medications: 18-month follow-up.

IMPORTANCE: Additional data are sought regarding treatment options for glaucoma, a major cause of global blindness. BACKGROUND: The study assessed outcomes following standalone implantation of two second-generation trabecular micro-bypass stents and postoperative topical prostaglandin in eyes with open-angle glaucoma not controlled on two preoperative medications. DESIGN: The study design is a prospective, nonrandomized, open-label study at a tertiary-care ophthalmology centre. PARTICIPANTS: Subjects had open-angle glaucoma with preoperative intraocular pressure of 18-30 mmHg on two medications, a medication washout phase, and post-washout intraocular pressure of 22-38 mmHg. All subjects (N = 53) have been followed for 18 months. METHODS: One day following implantation of two second-generation trabecular micro-bypass stents, subjects started topical travoprost. Medication washout was repeated at month 12. MAIN OUTCOME MEASURES: The main outcome measure was the proportion of eyes with intraocular pressure reduction ≥ 20% versus medicated baseline intraocular pressure with reduction of one medication at 12 months. RESULTS: At 12 months, 91% of eyes achieved intraocular pressure reduction ≥ 20% with reduction of one medication. All eyes had intraocular pressure ≤ 18 mmHg with reduction of one medication, and 87% had intraocular pressure ≤ 15 mmHg. Mean intraocular pressure on one medication was ≤ 13.0 mmHg (≥ 34% reduction) through 18 months. Mean post-washout intraocular pressure at month 13 was 33% lower than preoperative unmedicated intraocular pressure. No adverse events occurred through 18 months. CONCLUSIONS AND RELEVANCE: In open-angle glaucoma eyes on two preoperative medications, treatment with two second-generation trabecular stents and one postoperative prostaglandin resulted in mean intraocular pressure ≤ 13 mmHg with reduction of one medication, with favourable safety. These findings show the utility of second-generation trabecular bypass with postoperative prostaglandin in patients with open-angle glaucoma.

The Philadelphia Glaucoma Detection and Treatment Project: Detection Rates and Initial Management.

PURPOSE: To evaluate the detection rates of glaucoma-related diagnoses and the initial treatments received in the Philadelphia Glaucoma Detection and Treatment Project, a community-based initiative aimed at improving the detection, treatment, and follow-up care of individuals at risk for glaucoma. DESIGN: Retrospective analysis. PARTICIPANTS: A total of 1649 individuals at risk for glaucoma who were examined and treated in 43 community centers located in underserved communities of Philadelphia. METHODS: Individuals were enrolled if they were African American aged ≥50 years, were any other adult aged ≥60 years, or had a family history of glaucoma. After attending an informational glaucoma workshop, participants underwent a targeted glaucoma examination including an ocular, medical, and family history; visual acuity testing, intraocular pressure (IOP) measurement, and corneal pachymetry; slit-lamp and optic nerve examination; automated visual field testing; and fundus color photography. If indicated, treatments included selective laser trabeculoplasty (SLT), laser peripheral iridotomy (LPI), or IOP-lowering medications. Follow-up examinations were scheduled at the community sites after 4 to 6 weeks or 4 to 6 months, depending on the clinical scenario. MAIN OUTCOME MEASURES: Detection rates of glaucoma-related diagnoses and types of treatments administered. RESULTS: Of the 1649 individuals enrolled, 645 (39.1%) received a glaucoma-related diagnosis; 20.0% (n = 330) were identified as open-angle glaucoma (OAG) suspects, 9.2% (n = 151) were identified as having narrow angles (or as a primary angle closure/suspect), and 10.0% (n = 164) were diagnosed with glaucoma, including 9.0% (n = 148) with OAG and 1.0% (n = 16) with angle-closure glaucoma. Overall, 39.0% (n = 64 of 164) of those diagnosed with glaucoma were unaware of their diagnosis. A total of 196 patients (11.9%) received glaucoma-related treatment, including 84 (5.1%) who underwent LPI, 13 (0.8%) who underwent SLT, and 103 (6.2%) who were prescribed IOP-lowering medication. CONCLUSIONS: Targeting individuals at risk for glaucoma in underserved communities in Philadelphia yielded a high detection rate (39.1%) of glaucoma-related diagnoses. Providing examinations and offering treatment, including first-line laser procedures, at community-based sites providing services to older adults are effective to improve access to eye care by underserved populations.

Reversible structural and functional changes after intraocular pressure reduction in patients with glaucoma.

PURPOSE: The aim of this study was to evaluate structural and functional improvement following intraocular pressure (IOP) reduction in patients with glaucoma using Spectral Domain Optical Coherence Tomography (SD-OCT), Visual Field (VF) testing, and Visual Evoked Potentials (VEP). METHODS: A total of 76 eyes from 61 patients underwent SD-OCT, VF and VEP testing. Sixty-two eyes were put in either an acutely high (group 1, IOP > 32 mmHg) or mildly high (group 2, IOP between 22 and 31 mmHg) IOP group and underwent a pressure-lowering intervention. Fourteen eyes with stable glaucoma were controls (group 3, IOP < 22 mmHg). SD-OCT, VF and VEP testing were subsequently performed on all patients at three follow-up visits. Results from these follow-up periods were analyzed for signs of functional and structural improvement. RESULTS: Both group 1 and group 2 patients demonstrated significant decrease in the average cup to disc ratio (p < 0.05) following the intervention. Post-interventional reduction of cup volume was also significant for group 2 patients (p < 0.05). RNFL thickness changes were insignificant. Qualitative grading of VFs by two observers showed improvement in group 1 patients' VFs (p = 0.021). VEP measurements were mostly insignificant, with the exception of High Contrast Latency (LHC) deteriorating for group 2 patients in the first follow-up visit (p = 0.025). CONCLUSIONS: This study provides evidence for structural disc cupping reversal following IOP lowering interventions. These changes were not related to the amount of pressure lowering. While there was evidence of functional improvement as measured by VF testing, VEP was unable to detect any reversible changes.

Repeatability of selective laser trabeculoplasty for open-angle glaucoma.

BACKGROUND: To analyze the results of repeat selective laser trabeculoplasty (SLT). INCLUSION CRITERIA: participants with primary or secondary open-angle glaucoma (excluding uveitic) who had undergone SLT 360° (SLT 1) with diminution of response over time followed by repeat SLT 360° (SLT 2). Six months of follow-up were required and at least 6 months in between SLT 1 and 2. The main outcome measures were IOP reduction at 6 and 12 months and a comparison of the response between SLT 1 and 2. RESULTS: One hundred thirty-seven patients met the inclusion criteria. If only one eye had repeat treatment, that eye was chosen; if both eyes qualified, one was chosen at random. The baseline intraocular pressure (IOP) for SLT 1 = 20.3+/- 5.2 mmHg and SLT 2 = 19.4 +/- 5.0 was reduced to 16.4 +/- 3.9 and 16.7 +/- 4.7 at 1 year, respectively (p < .001). Medication use was not significantly changed, and was 2.2 +/- 1.2 at baseline for SLT 1 and 2.1 +/- 1.3 for SLT 2, and at 1 year was 1.9 +/- 1.3 and 2.2 +/- 1.2, respectively. A subanalysis of 62 patients matched for equivalent baselines showed a baseline IOP = 18.7 +/- 3.8 for SLT 1 and 18.7 +/- 3.5 for SLT 2, reduced to 16.0 +/- 4.3 and 15.3 +/- 3.8 at 1 year (p < .001). CONCLUSION: Repeat SLT laser (360-degree treatment, followed by a loss of effect over time, then a second 360-degree treatment) in this population resulted in IOP lowering similar to that of the initial treatment.

Barriers to Receiving Follow-Up Eye Care and Detection of Non-Glaucomatous Ocular Pathology in the Philadelphia Glaucoma Detection and Treatment Project.

This cross-sectional study aimed to evaluate adherence rates and identify barriers to receiving follow-up eye care in participants diagnosed with significant non-glaucomatous eye pathology in the Philadelphia Glaucoma Detection and Treatment Project. This community-based project aimed to improve detection, management, treatment, and follow-up eye care of individuals at high risk for glaucoma in community-based settings. Participants throughout Philadelphia, Pennsylvania, USA were enrolled. After a comprehensive eye examination, follow-up recommendations were given to each participant. A telephone survey was administered to individuals diagnosed with non-glaucomatous ocular pathology 3 months after initial eye examination to assess rates of follow-up and to evaluate potential barriers to follow-up. Of the 1649 participants enrolled in this project, 249 (15 %) were diagnosed with significant non-glaucomatous ocular pathology requiring follow-up care. There were 143 (57 %) who responded to the telephone survey. Respondents had a median age of 72 years, and were predominately female (69 %) and African-American (64 %). Of the respondents, 36 (25 %) attended a follow-up appointment. Participants who did not remember the results of their examinations, did not remember their recommendations, and had not seen an eye doctor within the past year were less likely to make a follow-up appointment (P = 0.04, 0.001 and 0.005, respectively). The Philadelphia Glaucoma Detection and Treatment Program was able to detect a significant amount of non-glaucomatous ocular pathology requiring follow-up care. Actual follow-up rates were sub-optimal. Further research is needed to determine interventions to overcome barriers and increase adherence with follow-up recommendations.

Unilateral Prostaglandin-Associated Periorbitopathy: A Syndrome Involving Upper Eyelid Retraction Distinguishable From the Aging Sunken Eyelid.

PURPOSE: To study the effects of prostaglandin analogue drops on the eyelids and adnexa in unilaterally treated subjects with the intention of qualifying, quantifying, and categorizing the characteristics of prostaglandin-associated periorbitopathy (PAP). METHODS: Patients using prostaglandin analogue drops in only 1 eye for at least 1 year were evaluated by masked examiners. Orbital and eyelid measurements were obtained for each patient, and adnexal photographs were taken. PAP was divided into 3 grades based on the presence and severity of fat atrophy and the existence and depth of superior sulcus deformity. Statistical analysis was performed comparing data between treated and untreated eyes. RESULTS: Thirty-three patients meeting eligibility criteria were enrolled, with equal numbers of subjects using latanoprost, travoprost, and bimatoprost. Treated eyes had a statistically significant increase in lagophthalmos (0.62 mm, p < 0.001), superior sulcus deformity/PAP grade (0.72, p < 0.001), and eyelid redness (1.08, p < 0.001). Treated eyes had significantly greater marginal reflex distance 1 measurements (0.89 mm, p = 0.02), highest with bimatoprost and moderate PAP. Treated eyes had relatively greater enophthalmos than untreated eyes. Very few patients noticed or complained about eyelid changes. CONCLUSION: Prostaglandin analogue drops cause adnexal changes and orbital fat atrophy leading to eyelid redness, superior sulcus deformity, higher eyelid crease, and enophthalmos. In contrast to previous studies showing ptosis in PAP, relative upper eyelid retraction was seen in most of our treated eyes. Our novel PAP grading scale may help objectify and categorize this syndrome. Awareness of these signs is critical, as the eyelids and eyes may be affected even in the absence of patient recognition.

An overview of home tonometry and telemetry for intraocular pressure monitoring in humans.

PURPOSE: To review the existing technology for self-tonometry and evaluate methods for continuous monitoring of IOP currently undergoing development and clinical trials in humans. BACKGROUND: Glaucoma is one of the leading causes of blindness worldwide. Current glaucoma therapy is focused primarily on lowering intraocular pressures (IOP). Decisions to modify treatment regiments are primarily based on office IOP. Since IOP fluctuates throughout the day, values obtained in the office may be a poor representation of the patient's disease. IOP measurements outside of the physician's office environment would provide better knowledge of the disease state and allow for better-informed medical decision making. METHODS AND RESULTS: We performed a literature search using Medline and IEEE database for studies investigating technologies that have been developed for continuous 24-hour IOP monitoring. CONCLUSION: There is currently no technology that has been approved for use to allow for continuous monitoring of IOP fluctuations. New experimental technology being developed and currently undergoing clinical trials has demonstrated potential for changing the diagnosis and management of glaucoma.

Efficacy and Safety of the Travoprost Intraocular Implant in Reducing Topical IOP-Lowering Medication Burden in Patients with Open-Angle Glaucoma or Ocular Hypertension.

PURPOSE: A randomized, double-masked, multicenter, phase 2 trial to evaluate the long-term safety and efficacy of travoprost intraocular implant, an extended-release drug delivery system designed to provide uninterrupted sustained intraocular pressure (IOP)-lowering therapy, thereby reducing patient treatment burden and improving adherence with IOP-lowering medication. METHODS: Patients with open-angle glaucoma or ocular hypertension were administered a fast-eluting implant (FE implant, n = 51) and received twice-daily (BID) placebo eye drops, a slow-eluting (SE implant, n = 54) and received BID placebo eye drops, or underwent a sham surgical procedure and received BID timolol 0.5% (n = 49). IOP was measured at baseline, day 1-2, day 10, week 4, week 6, month 3, and every 3 months thereafter through 36 months. Efficacy was evaluated by mean change from 8:00 AM unmedicated baseline IOP through month 36, and the percentage of patients receiving the same or fewer topical IOP-lowering medications as at screening (pre-study). Safety was evaluated by adverse events and ophthalmic parameters. RESULTS: Clinically and statistically relevant IOP-lowering treatment effects were observed through month 36 after a single administration of the travoprost implant compared with BID timolol with mean IOP reductions ranging from 7.6 to 8.8 mmHg for the FE implant group, from 7.3 to 8.0 mmHg for the SE implant group, and from 7.3 to 7.9 for the timolol group at the 8:00 AM timepoint (P < 0.0001 for all treatment groups at all visits). At months 12, 24, and 36, a greater percentage of FE and SE implant patients versus timolol patients were well controlled on the same or fewer topical IOP-lowering medications compared with screening with 63 and 69% for the FE and SE implants groups, respectively, versus 45% for the timolol group at month 36. The safety profile of the implant was favorable; there were no dislodgements, no explantations, no adverse events of conjunctival hyperemia or periorbital fat atrophy, no discontinuations due to study eye adverse events, nor any serious adverse events in the study eye. Comparable changes from baseline in corneal endothelial cell counts were observed in the three treatment groups over the 36 months. CONCLUSION: The travoprost intraocular implant demonstrated robust IOP-lowering and substantially reduced topical IOP-lowering medication burden for up to 36 months following a single administration, while maintaining a favorable safety profile. The travoprost intraocular implant promises to be a meaningful addition to the interventional glaucoma armamentarium by addressing the key shortcomings of topical IOP-lowering medications, including low adherence and topical side effects while controlling IOP for up to 36 months. TRIAL REGISTRY: ClinicalTrials.gov identifier NCT02754596 registered 28 April 2016.