An exploratory study to evaluate visual function endpoints in non-advanced age-related macular degeneration.

BACKGROUND: To prevent irreversible vision loss in age-related macular degeneration (AMD), it is critical to detect retinal dysfunction before permanent structural loss occurs. In the current study we evaluated a series of visual function tests to identify potential endpoints to detect visual dysfunction in non-advanced AMD. METHODS: A series of visual function tests were performed on 23 non-advanced AMD subjects (AREDS grade 1-4 on simplified scale) and 34 age-matched normals (AREDS grade 0). Tests included some commonly used endpoints such as ETDRS visual acuity (VA), low luminance (LL) 2.0ND ETDRS VA, MNREAD as well as newly developed tests such as the Ora-VCF™ test, Ora-tablet reading test, color sensitivity etc. Differences between the two groups were compared for each test. Test-retest repeatability and reproducibility was assessed on a subset of subjects and percent agreement was calculated. RESULTS: There was no difference in standard ETDRS VA between non-advanced AMD (0.06 ± 0.02 logMAR) and normal groups (0.04 ± 0.02 logMAR) (p = 0.57). LL 2.0 ETDRS VA and MNREAD showed no difference between the groups (p > 0.05). Ora-VCF™ test was significantly worse in the non-advanced AMD group compared to normals (0.67 ± 0.07 in AMD; 0.45 ± 0.04 in normals, p = 0.005). Non-advanced AMD subjects also had significantly worse reading performance using the Ora-tablet with LL 2.0ND (114.55 ± 11.22 wpm in AMD; 145.17 ± 9.55 wpm in normals p = 0.049). No significant difference between the groups was noted using other tests. Repeatability was 82% for Ora-VCF™ test and 92% for Ora-tablet LL 2.0ND reading. Reproducibility was 89% for both Ora-VCF™ test and Ora-tablet LL 2.0ND reading. CONCLUSION: While there was no significant difference between non-advanced AMD and normal groups using some current common endpoints such as ETDRS VA, LL 2.0 ETDRS VA or MNREAD, Ora-VCF™ test and Ora-tablet LL 2.0ND reading tests were able to identify significant visual dysfunction in non-advanced AMD subjects. These tests show promise as endpoints for AMD studies.

Early Ophthalmic Changes in Macula Does Not Correlate with Visual Function.

PURPOSE: Early detection and treatment of age-related macular degeneration require a clear understanding of the early progress of the disease. The purpose of this study was to investigate whether minimal macular ophthalmoscopic changes corresponded to changes in visual function. METHODS: Color macular photos from a group of older subjects who were classified as grade 0 on AREDS simplified grading were further evaluated by a retinal specialist using 5x magnification for possible minimal macular anomalies. Group 0-A (N = 15) were defined as subjects with no visible macular anomalies while Group 0-B (N = 19) comprised subjects for whom minimal macular mottling, pigment changes or very small drusen (< 63 µm) were observed in the study eye. All subjects had best VA of 20/25 or better and had no evidence of other retinal diseases in the study eye. All subjects underwent a series of visual function tests such as standard ETDRS VA, low luminance ETDRS VA, Pelli-Robson contrast sensitivity, variable contrast flicker (VCF) sensitivity, and reading speed (words per minute, wpm) using both MNRead and low luminance reading on a tablet. RESULTS: There was no significant difference between the mean age between the two groups (74.8 ± 5.2 years for 0-A vs 74.5 ± 4.4 for 0-B, p = 0.82). None of the visual function tests identified any significant difference between the two groups. Mean ETDRS VA was 0.0 ± 0.11 for 0-A subjects and 0.08 ± 0.12 for 0-B (p = 0.063). Mean Pelli-Robson log contrast sensitivity was 1.75 ± 0.29 for 0-A and 1.78 ± 0.17 for the 0-B group (p = 0.73). VCF threshold was 0.47 ± 0.25 for 0-A and 0.43 ± 0.22 for 0-B (p = 0.64). Reading speed using MNRead was 214 ± 47.4 wpm for 0-A and 210 ± 64.7 for 0-B (p = 0.85). Low luminance tablet reading speed was 137 ± 71.8 wpm for 0-A and 151 ± 39.4 (0-B) (p = 0.49). CONCLUSION: A panel of psychophysical tests did not demonstrate significant differences between subjects with and without minimal macular changes.

Clinical evaluation of a superabsorbent polymer dressing in enabling self-care of wounds.

Patient involvement in their own treatment can enable those with wounds in the community to play an active role in the management of their condition by, for example, completing dressing changes between health professional visits. The original primary study was undertaken to assess the clinical effectiveness of Zetuvit Plus Silicone Border (ZPSB) on exudate management. This retrospective sub-group analysis is aimed to demonstrate the effectiveness of a superabsorbent polymer (SAP) dressing (ZPSB) in enabling patients or their carers to undertake unsupervised dressing changes on their own. ZPSB was found to be clinically effective in this subgroup of patients, while also having additional features that enabled the patient to self-care. Overall, ZPSB enabled the patient to be part of their treatment plan and play an active role in the care of their wounds, thereby promoting self-care. This had a positive effect on nursing time saving and patient satisfaction.

An Alternative Psychophysical Diagnostic Indicator of the Aging Eye.

PURPOSE: Impaired adaptation to changes in lighting levels as well as mesopic visual function is a common complaint in those over the age of 65. The use of photostress is a well-established method to test the adaption rate and the response of the visual cycle. In this study, we test visual function recovery to mesopic luminance stimuli following a long duration photostress in young and elderly subjects. If successful in strongly differentiating aging macular function, these methods may also be useful in the study of pathologies such as age-related macular degeneration. METHODS: A group of 12 older normal subjects (mean age 75.1 ± 4.79) and a control group of 5 younger normal subjects (mean age 26.2 ± 4.19) were subjected to macular photostress using the OraLux photostress system. The OraLux system provides a diffuse light source bleaching 84% of cone photopigment while maintaining an exposure safety factor of 200 times less than the maximum safe exposure. After each photostressing session, macular recovery was tracked using a foveal, variable contrast, flickering stimulus of mean luminance in the high mesopic range. Recovery was tracked for 300 seconds. The endpoint was time to recovery to each individual's baseline sensitivity as determined by two static sensitivity trials prior to photostress. RESULTS: Proportional hazards analysis of recovery time yielded a statistically significant difference between the older group and the young group (HR = 0.181; p=0.0289). The estimated hazard ratio of 0.181 indicates that older subjects return to baseline at less than one-fifth the rate of younger subjects. The hazards ratio remained statistically significant after adjusting for visual acuity (HR = 0.093; p=0.0424). CONCLUSION: Photostress recovery of flicker sensitivity under mesopic conditions is a strong differentiator of aging macular function. This agrees with subject-reported complaints in reduced luminance conditions after exposure to bright lights such as night driving. The qualitative similarity between the aging retina and changes in early AMD suggests that flicker recovery following photostress may be useful as a surrogate endpoint in AMD clinical trials.

Efficacy and Toxicity of Every 2 Weeks Docetaxel Regimen in Comparison With Weekly or Every 3 Weeks in Metastatic Prostate Cancer: A Retrospective Analysis.

OBJECTIVES: The aim of this study was to compare weekly (q1w), 2 weekly (q2w), and 3 weekly (q3w) regimens of docetaxel in metastatic castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: We retrospectively studied patients treated with q1w, q2w, or q3w docetaxel regimens at 30, 60, and 75 mg/m, respectively. The choice and duration of treatment was decided by their oncologist. Patients were assessed for response, progression-free survival (PFS), and overall survival (OS), and toxicity. RESULTS: Twelve, 14, and 15 patients were in the q1w, q2w, and q3w arms, respectively. Patients' age, metastases, and mean prostate-specific antigen at start and nadir were similar among groups. Mean total dose (MTD) was higher (not significantly) in the q2w group. Response rates, mean, and median PFS and OS ranked q2w>q3w>q1w (not significantly). However, hazard ratios for PFS for the q2w and q3w arms were statistically superior to the q1w arm when adjusted for age and total dose. The same was true for OS when q3w was compared with q1w. There were no significant differences between the q2w and q3w arms. Toxicities were not different between any of the arms, save for grade 1/2 neuropathy (lower in q1w compared with q2w). CONCLUSIONS: The MTD, response rates, PFS, and OS in the q1w and q3w arms were similar to published reports. Although we had a small number of patients, our findings suggest that both dose concentration and total docetaxel dose may be important in the treatment of CRPC and q2w dosing is an option in patients intolerant of a higher dose concentration.

Exacerbation of signs and symptoms of allergic conjunctivitis by a controlled adverse environment challenge in subjects with a history of dry eye and ocular allergy.

BACKGROUND: The goal of this study was to assess the effect of a controlled adverse environment (CAE) challenge on subjects with both allergic conjunctivitis and dry eye. METHODS: Thirty-three subjects were screened and 17 completed this institutional review board-approved study. Subjects underwent baseline ocular assessments and conjunctival allergen challenge (CAC) on days 0 and 3. Those who met the ocular redness and itching criteria were randomized to receive either the controlled adverse environment (CAE) challenge (group A, n = 9) or no challenge (group B, n = 8) at day 6. Thirty minutes after CAE/no-CAE, subjects were challenged with allergen and their signs and symptoms graded. Exploratory confocal microscopy was carried out in a subset of subjects at hourly intervals for 5 hours post-CAC on days 3 and 6. RESULTS: Seven minutes post-CAC, subjects exposed to the CAE had significantly greater itching (difference between groups, 0.55 ± 0.25, P = 0.028), conjunctival redness (0.59 ± 0.19, P = 0.002), episcleral redness (0.56 ± 0.19, P = 0.003) and mean overall redness (mean of conjunctival, episcleral, and ciliary redness, 0.59 ± 0.14, P < 0.001). The mean score at 7, 15, and 20 minutes post-CAC for conjunctival redness (0.43 ± 0.17, P = 0.012), episcleral redness (0.49 ± 0.15, P = 0.001), mean overall redness in all regions (0.43 ± 0.15, P = 0.005), and mean chemosis (0.20 ± 0.08, P = 0.017) were also all significantly greater in CAE-treated subjects. Confocal microscopic images of conjunctival vessels after CAC showed more inflammation in CAE-treated subjects. CONCLUSION: In subjects with both dry eye and allergic conjunctivitis, exposure to adverse environmental conditions causes an ocular surface perturbation that can intensify allergic reactions.

Ocular iontophoresis of EGP-437 (dexamethasone phosphate) in dry eye patients: results of a randomized clinical trial.

PURPOSE: To assess safety and efficacy of EGP-437 (dexamethasone phosphate 40 mg/mL [DP]) in dry eye patients. METHODS: The study employed a prospective, single-center, double-masked design utilizing a Controlled Adverse Environment (CAE). Patients (n = 103) with confirmed signs and symptoms of dry eye syndrome were randomized into 1 of 3 iontophoresis treatment groups: 7.5 mA-min at 2.5 mA (DP 7.5, n = 41); 10.5 mA-min at 3.5 mA (DP 10.5, n = 37); or 10.5 mA-min at 3.5 mA (placebo, n = 25). Three CAE visits and 4 follow-up visits occurred over 3 weeks. Patients meeting enrollment criteria received iontophoresis in both eyes after the second CAE exposure (visit 3) and before the third CAE exposure (visit 5). Primary efficacy endpoints were corneal staining and ocular discomfort. Secondary endpoints included tear film break-up time, ocular protection index (OPI), and symptomatology. RESULTS: The DP 7.5 and DP 10.5 treatment groups showed statistically significant improvements in signs and symptoms of dry eye at various time points; however, the primary endpoints were not achieved. The DP 7.5 treatment group exhibited statistically significant improvements in corneal staining (when comparing the differences between study entry and exit, 3 weeks, P = 0.039), OPI (immediately following the second treatment, P = 0.048) and ocular discomfort at follow-up visits (a week after the first treatment, P = 0.032; 24 hours after the second treatment, P = 0.0032). Treatment-emergent adverse events (AEs) were experienced by 87% of patients and were consistent across all treatment groups. Most AEs were mild and no severe AEs were observed. CONCLUSION: Ocular iontophoresis of EGP-437 demonstrated statistically and clinically significant improvements in signs and symptoms of dry eye syndrome within a CAE model.

The Ocular Protection Index.

The interaction of the time between blinks, or the interblink interval (IBI), and tear film breakup time (TFBUT) helps to regulate the integrity of the ocular surface. A protected surface exists when the TFBUT matches or exceeds the IBI. In contrast, an unprotected surface exists when TFBUT is less than the IBI. This is clinically relevant because repeated intermittent exposure of a tear film-deficient cornea can lead to ocular discomfort and the development of clinical signs, such as keratitis and redness. The relationship between TFBUT and IBI has been quantified by the Ocular Protection Index (OPI), which is calculated by dividing TFBUT by IBI. If the OPI is <1.0, the patient has an exposed ocular surface, putting them at risk for the development of the signs and symptoms of dry eye, whereas if the OPI is >or=1.0, the patient's ocular surface is tear film protected. The OPI has proven to be useful in assessing the factors that may cause or exacerbate dry eye. This review discusses the development and use of the OPI model, its relationship to dry eye, and factors that are known to alter blink rate and tear film integrity.

Methodologies for the study of ocular surface disease.

The ability to obtain reliable results from clinical trials of therapies for ocular allergic disease and dry eye disease is often limited because of inadequate control of variables, such as environment, patient life style, compliance, and individual fluctuations that occur from one assessment visit to another. The controlled allergen challenge (CAC) model of allergic conjunctivitis allows signs and symptoms of the disease to be elicited in a physiologically accurate and reproducible manner. The rigid criteria for subject selection, the controlled allergic reaction, and the standardized and quantified grading systems allow for a reproducible baseline from which statistically and clinically significant differences between formulations can be assessed. Similarly, the controlled adverse environment (CAE) model for dry eye mimics the environmental stimuli that lead to ocular surface drying. Preselected subjects have a reproducible, homogeneous baseline reaction from which the effects of various treatments can be significantly evaluated and compared. CAC and CAE provide accurate means to study highly variable and individual ocular surface disease.

Evaluation of the comfort of Alphagan P compared with Alphagan in irritated eyes.

The tolerability of brimonidine tartrate 0.15%--referred to as bromonidine-Purite 0.15% in this study--was compared with brimonidine tartrate 0.2% in irritated eyes of healthy volunteers as well as patients with glaucoma or ocular hypertension (N=20) in a 2-week, single-center, randomized, double-masked, crossover study. Participants were evaluated at days 0, 7, 11, and 15. At day 0, they were exposed to a controlled adverse environment (CAE), in which humidity, temperature, and airflow was regulated, for up to 90 minutes. Participants who reported a sufficient level of bilateral ocular discomfort during exposure to the CAE were enrolled in this study and received 1 drop of brimonidine-Purite 0.15% in 1 eye and 1 drop of brimonidine tartrate 0.2% in the contralateral eye. Immediately following instillation, participants were asked to indicate their preference for either study medication. The study medications were not used between days 0 and 7. From day 7 to 10, participants administered either drug bilaterally. On day 11, the treatment was crossed over, and participants were asked to compare the preferred medication with their previous regimen. They continued to administer the drug bilaterally twice daily until day 15, when the preferred medication was again compared with the previous regimen. Following CAE exposure at visit 1, 70.6% of the participants preferred brimonidine-Purite 0.15% over brimonidine tartrate 0.2% and indicated that it was significantly more comfortable than brimonidine tartrate 0.2% (P=.009). When given brimonidine-Purite 0.15% first before switching to brimonidine tartrate 0.2%, 80% of participants preferred brimonidine-Purite 0.15% (P=.012). When given brimonidine tartrate 0.2% first before switching to brimonidine-Purite 0.15%, 85% preferred brimonidine-Purite 0.15% (P=.001). The results of this study suggest that brimonidine-Purite 0.15% is significantly more comfortable than brimonidine tartrate 0.2% in patients with irritated eyes.