Patients with Low Vision Struggle with Placing Eye Drops and Benefit from an Eye Drop Aid.

PURPOSE: To evaluate eye drop self-administration in a low-vision patient population and test whether a nose-pivoted drop delivery device (NPDD, GentleDrop) can improve eye drop delivery in these patients. DESIGN: Repeated-measures case series. PARTICIPANTS: Thirty subjects (58 eyes) with low vision, defined as best-corrected visual acuity worse than 20/60 or visual field worse than 20° in the better-seeing eye. METHODS: We video-recorded subjects while self-administering eye drops using their own traditional delivery at baseline, after a standardized teaching, and with an NPDD. Two masked graders independently reviewed each drop delivery. Primary success was defined as the drop reaching the eye without the bottle touching the eye or eyelids. Subjects rated ease-of-use (1-10 scale, 10 = easiest) after each drop delivery and completed a satisfaction survey, which included asking whether subjects could place drops independently (1-5 scale, 5 = most independent). MAIN OUTCOME MEASURES: Logistic-transformed generalized estimating equation regression to compare technique satisfaction, ease-of-use, independence, no contact, and success. RESULTS: Primary success was observed in 30 (52%) of 58 eyes at baseline and increased to 44 eyes (76%) with an NPDD (P = 0.013). Bottle tip contact occurred in 23 (40%) of 58 eyes at baseline and 8 eyes (14%) with an NPDD (P = 0.004). Mean ease-of-use scores were 6.7 ± 3.1 at baseline and 8.3 ± 1.8 (P < 0.001) with an NPDD. Likewise, the NPDD improved success, bottle tip contact, and ease-of-use compared with post-teaching traditional delivery (P < 0.01). Twenty-two (73%) of 30 subjects preferred the NPDD to traditional delivery. Twenty-nine (97%) thought the NPDD was comfortable to use, and all would recommend the device. A subgroup analysis was performed on 16 subjects that self-reported difficulty instilling drops at baseline. The NPDD showed similar results, and it increased confidence in placing drops independently (4.6 ± 0.9) compared with baseline (2.7 ± 1.6, P < 0.001). Fifteen (94%) subjects in this subgroup preferred the NPDD. CONCLUSIONS: Low-vision subjects struggled to self-administer eye drops. An NPDD can improve bottle tip contact, ease-of-use, satisfaction, and independence. Eye care providers could consider screening low-vision patients about difficulty with eye drop self-administration and recommending eye drop aids. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Eye Drop Adherence With an Eye Drop Bottle Cap Monitor.

PRCIS: An eye drop bottle cap monitor with audio and visual alarms measured eye drop adherence in 50 subjects with glaucoma. Baseline adherence rates were too high to test if the alarms could improve adherence. PURPOSE: To determine if an eye drop bottle cap monitor can measure and improve adherence. MATERIALS AND METHODS: The Devers Drop Device (D3, Universal Adherence LLC) was designed to measure eye drop adherence by detecting bottle cap removal and replacement, and it can provide text, visual and audio alerts when a medication is due. In Stage 1, we determined baseline adherence for 50 subjects using a nightly eye drop over a 25-day period. Subjects with less than 90% baseline adherence were eligible for Stage 2. In Stage 2, we randomized subjects to receive either no reminder or automated D3 alerts for their nightly eye drop over a subsequent 25-day period. We defined adherence as the proportion of drops administered within 3 hours of the subjects' scheduled dosing time. Subjects completed 3 questions regarding satisfaction with the device and willingness to pay. RESULTS: The D3 monitor remained attached to the eye drop bottle cap for the duration of the study and collected adherence data in all 50 patients. In Stage 1, the mean adherence rate was 90 ± 18% (range 32-100%). Forty (80%) subjects had an adherence rate greater than 90%. Adherence rates were too high in Stage 1 to adequately test the effects of reminders in Stage 2. Ninety-eight percent (49/50) and 96% (48/50) of subjects agreed "the device always stayed attached to the bottle cap" and "I was able to use the device to take the drops", respectively. Patients would pay $61±83 (range $0-400) for a similar device to improve adherence. CONCLUSIONS: The D3 can measure eye drop adherence. Research subjects reported high satisfaction and willingness to pay for an eye drop bottle cap monitor. Glaucoma patients have high adherence when they are being monitored, and future studies with research subjects screened for poor adherence may further determine the benefit of electronic monitoring of adherence with and without electronic reminders.

Optic nerve cavitations in glaucoma suspect and glaucoma patients.

Purpose: Glaucoma is associated with structural changes of the optic nerve head such as deformation, lamina cribosa defects, prelaminar schisis, and peripapillary retinal schisis. We describe optic nerve cavitations that were detected by routine spectral domain optical coherence tomography (OCT). Observations: OCT imaging showed cavitations in 5 eyes of 4 patients with an initial diagnosis of glaucoma or glaucoma suspect. The cavitations were seen as hyporeflective spaces that are sharply delineated from surrounding tissue. They were centered inferonasally, anterior to the lamina cribosa, and at least partially within the Bruch's membrane opening (BMO). They extended from 3 to 6 clock hours. Conclusion: AND IMPORTANCE: We describe a new OCT finding in patients with a diagnosis of glaucoma and glaucoma suspect. While previous reports describe cavitations in the choroid in patients with pathological myopia, our patients had minimal refractive error and the cavitations were located within the optic nerve. We will examine these patients over time to determine the impact of this finding on longitudinal changes in structure and function.

Intraocular Pressure and Medication Burden With Cataract Surgery Alone, or Cataract Surgery Combined With Trabecular Bypass or Goniotomy.

PRCIS: When compared with cataract surgery in glaucoma patients, trabecular micro-bypass and goniotomy resulted in a large decrease in the incidence of intraocular pressure (IOP) spikes, a modest effect on IOP, and a minimal effect on medication burden. PURPOSE: To compare changes in IOP and ocular hypotensive medications in 3 surgical cohorts: cataract surgery, cataract surgery with trabecular micro-bypass (cataract/trabecular), and cataract surgery with goniotomy (cataract/goniotomy). MATERIALS AND METHODS: We included 138 eyes diagnosed with open-angle glaucoma: (1) 84 eyes with cataract surgery alone, (2) 25 eyes with cataract/trabecular surgery, and (3) 29 eyes with cataract/goniotomy surgery. We compared the groups for postoperative IOP and the number of ocular hypotensive medications. We adjusted for preoperative IOP, and preoperative and postoperative number of ocular hypotensive medications. We defined an IOP spike as IOP ≥21 mm Hg and 10 mm Hg higher than preoperative on postoperative day 1. RESULTS: All 3 surgeries showed a decrease in IOP (P≤0.004) and medication burden (P≤0.001) at 3 and 6 months postoperatively when compared with their own preoperative baselines. When compared with cataract surgery alone, cataract/trabecular and cataract/goniotomy had similar IOP lowering at 1 month postoperatively, and variable results at 3 and 6 months. The change in ocular hypotensive medications was not statistically different between the surgical groups at any postoperative visit. Cataract/trabecular and cataract/goniotomy decreased IOP on postoperative day 1, and had relative risk reduction of ~70% for IOP spikes (P≤0.001 for both). CONCLUSION: Trabecular micro-bypass and goniotomy when added to cataract surgery resulted in a large decrease in IOP spikes, a modest effect on IOP, and a minimal effect on medication burden when compared with cataract surgery alone in glaucoma patients.

Clinicians' Use of Quantitative Information while Assessing the Rate of Functional Progression in Glaucoma.

PURPOSE: Clinicians use both global and point-wise information from visual fields to assess the rate of glaucomatous functional progression. We asked which objective, quantitative measures best correlated with subjective assessment by glaucoma experts. In particular, we aimed to determine how much that judgment was based on localized rates of change vs. on global indices reported by the perimeter. DESIGN: Prospective cohort study. PARTICIPANTS: Eleven academic, expert glaucoma specialists independently scored the rate of functional progression, from 1 (improvement) to 7 (very rapid progression), for a series of 5 biannual clinical printouts from 100 glaucoma or glaucoma suspect eyes of 51 participants, 20 of which were scored twice to assess repeatability. METHODS: Regression models were used to predict the average of the 11 clinicians' scores based on objective rates of change of mean deviation (MD), visual field index (VFI), pattern standard deviation (PSD), the Nth fastest progressing location, and the Nth fastest progressing of 10 anatomically defined clusters of locations after weighting by eccentricity. MAIN OUTCOME MEASURES: Correlation between the objective rates of change and the average of the 11 clinicians' scores. RESULTS: The average MD of the study eyes was -2.4 dB (range, -16.8 to +2.8 dB). The mean clinician score was highly repeatable, with an intraclass correlation coefficient of 0.95. It correlated better with the rate of change of VFI (pseudo-R2 = 0.73, 95% confidence interval [CI, 0.60-0.83]) than with MD (pseudo-R2 = 0.63, 95% CI [0.45-0.76]) or PSD (pseudo-R2 = 0.41, 95% CI [0.26-0.55]). Using point-wise information, the highest correlations were found with the fifth-fastest progressing location (pseudo-R2 = 0.71, 95% CI [0.56-0.80]) and the fastest-progressing cluster after eccentricity weighting (pseudo-R2 = 0.61, 95% CI [0.48-0.72]). Among 25 eyes with an average VFI of > 99%, the highest observed pseudo-R2 value was 0.34 (95% CI [0.16-0.61]) for PSD. CONCLUSIONS: Expert academic glaucoma specialists' assessment of the rate of change correlated best with VFI rates, except in eyes with a VFI near the ceiling of 100%. Sensitivities averaged within clusters of locations have been shown to detect change sooner, but the experts' opinions correlated more closely with global VFI. This could be because it is currently the only index for which the perimeter automatically provides a quantitative estimate of the rate of functional progression.

Clinicians' Use of Quantitative Information When Assessing the Rate of Structural Progression in Glaucoma.

PURPOSE: OCT scans contain large amounts of information, but clinicians often rely on reported layer thicknesses when assessing the rate of glaucomatous progression. We sought to determine which of these quantifications most closely relate to the subjective assessment of glaucoma experts who had all the diagnostic information available. DESIGN: Prospective cohort study. PARTICIPANTS: Eleven glaucoma specialists independently scored the rate of structural progression from a series of 5 biannual clinical OCT printouts. METHODS: A total of 100 glaucoma or glaucoma suspect eyes of 51 participants were included; 20 were scored twice to assess repeatability. Scores ranged from 1 (improvement) to 7 (very rapid progression). Generalized estimating equation linear models were used to predict the mean clinician score from the rates of change of retinal nerve fiber layer thickness (RNFLT) or minimum rim width (MRW) globally or in the most rapidly thinning of the 6 sectors. MAIN OUTCOME MEASURES: The correlation between the objective rates of change and the average of the 11 clinicians' scores. RESULTS: Average RNFLT within the series of study eyes was 79.3 µm (range, 41.4-126.6). Some 95% of individual clinician scores varied by ≤ 1 point when repeated. The mean clinician score was more strongly correlated with the rate of change of RNFLT in the most rapidly changing sector in %/year (pseudo-R2 = 0.657) than the rate of global RNFLT (0.372). The rate of MRW in the most rapidly changing sector had pseudo-R2 = 0.149. CONCLUSIONS: The rate of change of RNFLT in the most rapidly changing sector predicted experts' assessment of the rate of structural progression better than global rates or MRW. Sectoral rates may be a useful addition to current clinical printouts.

Prevalence and causes of clinically detectable uveitic serous retinal detachment.

PURPOSE: To describe the prevalence and causes of clinically detectable uveitic serous retinal detachment (SRD). METHODS: Retrospective chart review of a large clinic-based series. RESULTS: Serous retinal detachment was present in 78 of the 2761 (2.8%) patients. Vogt-Koyanagi-Harada (VKH) disease was the most commonly identified cause (38/78, 48.7%). Less common associated etiologies included toxoplasmic retinochoroiditis (8/78, 10.3%), sarcoidosis (5/78, 6.4%), intraocular lymphoma (4/78, 5.1%), presumed tuberculosis (3/78, 3.8%), and posterior scleritis (2/78, 2.6%). Fifteen patients (19.2%) with uveitic SRD at presentation had no identifiable etiology and were labeled idiopathic or indeterminant. Thirty of the 38 patients with VKH disease (78.9%) had positive neurological and/or integumentary findings, and therefore constituted either complete or incomplete subtypes of the disease. The remaining eight (21.1%) had presumed/ocular VKH disease limited to the eye. CONCLUSION: While VKH disease by far is the most common cause of clinically detectable uveitic SRD, a number of other non-infectious and infectious inflammatory disorders were also associated with this distinctive clinical finding.

Novel Eye Drop Delivery Aid Improves Outcomes and Satisfaction.

PURPOSE: To compare a nose-pivoted drop delivery device (NPDD) with traditional eye drop delivery in glaucoma subjects. DESIGN: Repeated-measures case series. PARTICIPANTS: Fifty glaucoma subjects (100 eyes) who reported difficulty self-administering eye drops. METHODS: We compared eye drop delivery using a NPDD against traditional delivery techniques at baseline (baseline traditional) and after standardized teaching (post-teaching traditional). Subjects used a 1-to-10 scale (10 being easiest) to rate the ease of delivery with each technique and completed a satisfaction survey. Two graders used digital video to independently review eye drop delivery and recorded: (1) accurate placement: the eye drop reached the ocular surface; (2) no contact: no bottle tip contact against the ocular or periocular surface; and (3)number of eye drops dispensed. We defined primary success as accurate placement and no contact; secondary success as primary success with only 1 drop dispensed. MAIN OUTCOME MEASURES: We used logistic-transformed generalized estimating equation (GEE) regression to compare technique satisfaction, accuracy, no contact, and primary and secondary success. Number of drops dispensed was compared using a Cox model. RESULTS: Forty-seven of 50 subjects (94%) preferred the NPDD over traditional eye drop delivery. The mean score for ease of use was higher for the NPDD (8.9 ± 1.1) than baseline traditional (6.7 ± 2.1; P < 0.001) and post-teaching traditional (7.0 ± 2.0; P < 0.001). Forty-nine of 50 (98%) subjects thought the NPDD was comfortable to use and would recommend the device. The eye drop reached the ocular surface in a similar percentage of subjects (>90%) with each method. The bottle tip contacted fewer eyes with the NPDD (10 eyes) than baseline traditional (33 eyes; P < 0.001) and post-teaching traditional (25 eyes; P = 0.009). The number of drops dispensed was lower with the NPDD (1.7 ± 1.2) than baseline traditional (2.2 ± 1.6; P = 0.017) and post-teaching traditional (2.4 ± 1.8; P = 0.006). The NPDD increased primary and secondary success of eye drop delivery (86% and 54%, respectively) compared to baseline traditional (66% [P = 0.001] and 28% [P < 0.001]) and post-teaching traditional (70% [P = 0.005] and 40% [P = 0.018]). CONCLUSIONS: Eye drop users preferred the NPDD over traditional eye drop delivery. The NPDD improved eye drop delivery success, reduced bottle tip contact, and decreased the number of eye drops wasted.

Glaucoma Specialist Detection of Optical Coherence Tomography Suspicious Rim Tissue in Glaucoma and Glaucoma Suspect Eyes.

PURPOSE: To assess glaucoma specialists' detection of optic nerve head (ONH) rim tissue that is thin by optical coherence tomography (OCT) criteria. DESIGN: Reliability analysis. METHODS: Five clinicians marked the disc margin (DM) and rim margin (RM) on stereophotographs of 151 glaucoma or glaucoma suspect eyes obtained within 3 months of OCT imaging. The photo and OCT infrared image for each eye were co-localized and regionalized into 12 sectors relative to the axis between the Bruch membrane opening (BMO) centroid and the fovea. For each clinician, the distance from BMO centroid to their DM (DM radius) and RM (RM radius) was used to generate sectoral rim width (RW) (DM radius-RM radius) and cup-to-disc ratio (CDR) (RM radius/DM radius) estimates. OCT minimum rim width (MRW) was determined by sector. Among all eyes, for each OCT MRW suspicious sector (<5% of OCT normative database), we determined each clinician's detection (clinician CDR ≥ 0.7). RESULTS: Clinicians most commonly failed to detect OCT suspicious rim tissue in the nasal sectors. Among 502 sectors with suspicious OCT MRW, all 5 clinicians rated CDR ≥ 0.7 in only 29.5% and all 5 clinicians rated CDR < 0.7 in 21%. OCT suspicious rim thickness was most common (32% of eyes) in the nasal and inferior sectors. MRW vs clinician RW discordance was greatest nasally, while BMO vs clinician DM discordance was greatest temporally. CONCLUSIONS: Clinicians most commonly failed to detect OCT suspicious rim thickness nasally where suspicious rim tissues were also most common.

Glaucoma Specialist Optic Disc Margin, Rim Margin, and Rim Width Discordance in Glaucoma and Glaucoma Suspect Eyes.

PURPOSE: To quantify the variability of 5 glaucoma specialists' optic disc margin (DM), rim margin (RM), and rim width (RW) estimates. DESIGN: Inter-observer reliability analysis. METHODS: Clinicians viewed stereo-photographs from 214 subjects with glaucoma or ocular hypertension and digitally marked the DM and RM. For each photograph, the centroid of each clinician's DM was calculated, and an averaged DMcentroid was determined. The axis between the DMcentroid and the fovea was used to establish 12 30-degree sectors. Measurements from the DMcentroid to each clinician's DM (DMradius) and RM (RMradius) were used to generate a RW (DMradius-RMradius) and cup-to-disc ratio (CDR) (RMradius/DMradius) by sector. Parameter means, standard deviations, and coefficient of variations (COVs) were calculated across all clinicians for each eye. Parameter means for each clinician, and intraclass correlation coefficients (ICC), were calculated across all eyes by sector. RESULTS: Among all eyes, the median COV by sector ranged from 3% to 5% for DMradius, 20% to 25% for RMradius, and 26% to 30% for RW. Sectoral ICCs for CDR ranged from 0.566 to 0.668. Sectors suspicious for rim thinning by 1 clinician were frequently overlooked by others. Among 1724 sectors in which at least 1 clinician was suspicious for rim thinning (CDR ≥ 0.7), all 5 clinicians' CDRs were ≥ 0.7 in only 499 (29%), and 2 of the 5 clinicians failed to detect rim thinning (CDR < 0.7) in 442 (26%). CONCLUSION: In this study, glaucoma specialist RM, DM, and RW discordance was frequent and substantial, even in sectors that were suspicious for rim thinning.

Concentration Accuracy of Compounded Mitomycin C for Ophthalmic Surgery.

IMPORTANCE: Ophthalmologists rely on accurate concentrations of mitomycin C (MMC) to prevent scarring with trabeculectomy surgery. To our knowledge, the concentration accuracy and variability of compounded MMC are unknown. OBJECTIVE: To determine whether the measured concentration differs from the expected concentration of 0.4 mg/mL of MMC used in ophthalmic surgery. DESIGN, SETTING, AND PARTICIPANTS: Laboratory experimental investigation conducted in July 2013. We acquired 60 samples of 0.4 mg/mL of MMC from a spectrum of common compounding and storage techniques (refrigeration, freezing, and immediately compounded dry powder) and a variety of pharmacies (an academic hospital, a community hospital, and an independent Pharmacy Compounding Accreditation Board-accredited pharmacy). We used C18 reversed-phase high-performance liquid chromatography to measure the MMC concentration of all samples. We used pure MMC (Medisca Inc) to generate calibration curves and sulfanilamide as an internal standard. MAIN OUTCOMES AND MEASURES: We calculated MMC concentration using a calibration curve (range, 0.3-0.5 mg/mL) generated by dividing MMC peak area by internal standard peak area and plotting the area ratio against the calibrant concentrations. We compared the measured concentration against the expected 0.4 mg/mL concentration for all samples. RESULTS: Measurement of MMC using the high-performance liquid chromatography method demonstrated acceptable accuracy (92%-100%), precision (2%-6% coefficient of variation), and linearity (mean correlation coefficient of r2 = 0.99). The measured MMC concentration determined using the high-performance liquid chromatography method for all samples was 12.5% lower than the expected 0.4 mg/mL value (mean [SD], 0.35 [0.04] mg/mL; 95% CI, 0.34-0.36; P < .001) with a wide concentration range between 0.26 and 0.46 mg/mL. CONCLUSIONS AND RELEVANCE: Common compounding and storage techniques for MMC resulted in a lower accuracy and wider range of concentration than expected. These differences in concentration may result from compounding techniques and/or MMC degradation. Variability in MMC concentration could cause inconsistency in glaucoma surgical results, but the clinical relevance of such findings on glaucoma surgery outcomes remains unknown.

The Degradation of Mitomycin C Under Various Storage Methods.

PURPOSE: To compare the effects of common pharmacy preparation and storage conditions on the stability of mitomycin C (MMC) in solution. METHODS: We used C18 reversed-phase high-performance liquid chromatography to determine the stability of 0.4 mg/mL MMC solutions, and liquid chromatography-electrospray ionization-mass spectrometry to identify degradation products. Conditions compared were: compounding and storage by refrigeration (1 and 2 wk), freezing (23 d), shipment "on-ice" (1 mo frozen followed by 1-wk refrigeration), and immediately compounding dry powder (Mitosol; Mobius Therapeutics LLC). We tested 3 samples for each storage method when samples reached room temperature (time 0), and then 1, 4, and 24 hours later. We used MMC peak area as a percentage of total (MMC plus degradants) area detected with high-performance liquid chromatography as a measure of stability. RESULTS: We assessed MMC stability for 5 preparation and storage methods at 4 timepoints (with n=3 per timepoint). At time 0, we found similar stabilities for MMC (F=0.72, P=0.599) between all 5 storage methods: 1-week refrigerated (97.9±0.2%), dry powder (97.5±0.3%), 2-week refrigerated (96.9±0.2%), 23-day frozen (96.7±3.1%), and shipment on-ice (96.0±1.2%). However, MMC demonstrated significant degradation over a 24-hour period with 2-week refrigeration (95.7±0.3%, ß=-0.1%/h, P<0.001) and shipment on-ice (93.1±1.8%, ß=-0.1%/h, P=0.013). We identified small amounts (<3.2%) of 2 degradants, cis-hydroxymitosene and trans-hydroxymitosene, across all samples. CONCLUSIONS: The different preparation and storage methods of MMC showed similar stability when used immediately upon reaching room temperature. However, degradation of MMC occurred with further storage at room temperature. The clinical implication of small amounts of MMC degradants is unclear.