Arshad M. Khanani

Day to day variability of the dark-adapted pupil diameter

Purpose: To determine the individual variability of the dark‐adapted pupil diameter over 2 testing sessions using a standardized dark‐adaptation protocol. Setting: Texas Tech University Health Sciences Center, Lubbock, Texas, USA. Methods: In this prospective observational cohort study, 40 volunteers with no history of ocular disease, surgery, or injury other than requirement for refractive correction were included. The right eye was tested. A standardized dark‐adaptation protocol was used that controlled for accommodation and patient alertness. Infrared, still digital photographs were taken after 5 and 10 minutes of dark adaptation and analyzed independently by 2 investigators using digital‐image software. Two test sessions were performed 1 to 7 days apart. Lifestyle factors such as sleep, diet, and exercise were not controlled. Results: The mean subject age was 31.5 years (range 20 to 49 years). There were 20 men; 27 subjects wore correction for myopia, and 13 wore no correction. The mean interval between test sessions was 2 days (range 1 to 7 days). The mean difference and 95% confidence intervals for pupil diameter difference between sessions were as follows: 5‐minute readings, +0.032 mm (−0.030 to +0.094); 10‐minute readings, −0.006 mm (−0.059 to +0.047); mean of 5‐ and 10‐minute readings, +0.013 mm (−0.038 to +0.064). Using the paired t test, the pupil diameter did not differ significantly between sessions in 5‐minute dark adaptation (P = .2980), 10‐minute dark adaptation (P = .8263), or the mean (P = .6049). Conclusion: Using a consistent dark‐adaptation protocol that controlled for alertness, individuals aged 20 to 49 years showed no significant variation in dark‐adapted pupil diameter when tested twice in 1 week.

Six-month variability of the dark-adapted pupil diameter

Purpose: To determine the individual variability of the dark‐adapted pupil diameter over 6 months using a standardized dark‐adaptation protocol. Setting: Texas Tech University Health Sciences Center, Lubbock, Texas, USA. Methods: This prospective observational cohort study comprised volunteers with no history of ocular disease, surgery, or injury other than requirement for refractive correction. The right eye was tested. A standardized dark‐adaptation protocol was used that controlled for accommodation and patient alertness. Infrared, still digital photographs were taken after 10 minutes of dark adaptation at 1 lux and were analyzed using digital image software. Testing was performed at baseline in the afternoon, at 3 months in the afternoon, and at 6 months in the morning. Lifestyle factors such as diet and exercise were not controlled. Results: Mean intersession differences were 0.04 mm (95% confidence interval [CI]: −0.68‐0.146), 0.15 mm (95% CI: −0.001‐0.297), and 0.09 mm (95% CI: −0.048‐0.236) for baseline–3 month, baseline–6 month, and 3 month–6 month comparisons, respectively. None of these differences was significantly different from zero (P>.05, 2‐tailed Student t tests). The likelihood that the mean intersession difference was >.25 mm was negligible for all comparisons (P = .9996, .9099, and .9829 respectively, 1‐tailed Student t tests). Conclusion: When a consistent dark‐adaptation protocol that controls for alertness and accommodation is used, normal young individuals showed no significant variation in the dark‐adapted pupil diameter over a 6‐month period.

Normal values for a clinical test of letter-recognition contrast thresholds

Purpose: To investigate the contrast thresholds (CTs) in normal subjects using a high‐luminance, letter‐recognition task under clinically relevant testing conditions. Setting: Texas Tech University Health Sciences System, Lubbock, Texas, USA. Methods: Sixty normal subjects aged 20 to 49 years with a best corrected visual acuity of 20/20 or better in both eyes participated. M & S Technologies software was used to display black‐on‐white Sloan letters at contrast levels of 25%, 20%, 15%, 12%, and 10% through 1% in 1% decrements. The effects of age, sex, optotype size, eye dominance, ambient illumination level (bright = 625 − 630 lux; dim = <3 lux), and direction of approach to threshold were analyzed using a multivariate, ordinary, least‐squares analysis. Results: Age and sex did not influence CTs. Ascending versus descending testing was not statistically significant (P>.5). The effects of room illumination and eye dominance were significant (P<.01). Significant differences were found between 20/30 and 20/50, 20/30 and 20/70, and 20/50 and 20/70 optotype sizes (P<.01 for all comparisons). Conclusions: A commercially available, computer‐based test of CTs was easy to administer and apparently easy for inexperienced subjects to perform. The results suggest criteria for detecting visual problems concerned with familiar but complex spatial‐image shapes. This information might be used to assess the effects of treatments such as laser refractive surgery on recognition contrast. Further study is warranted.

Horizontal versus vertical dark-adapted pupil diameters in normal individuals

Purpose: To determine the distribution of the difference between the horizontal and vertical dark‐adapted entrance pupil diameters (PDs) in normal individuals. Setting: Texas Tech University Health Sciences Center, Lubbock, Texas, USA. Methods: In this observational cohort study, high‐magnification infrared pupil photography was performed of the right eye of 26 normal volunteers from 20 to 47 years of age. The horizontal and vertical PDs were measured using commercially available digital‐image software, taking into account the effect of photographic parallax. Results: In 24 subjects (85%), the vertical PD was larger than the horizontal PD; in 8 subjects (31%), it was 0.30 mm to 0.50 mm larger. In 2 subjects, the horizontal diameter was slightly larger but the difference was <0.10 mm. The mean horizontal to vertical PD ratio was 0.97. Conclusions: In this study population, the vertical PD was larger than the horizontal PD in most subjects. Although the difference was a fraction of the total PD, it may be important for laser refractive surgery planning and preoperative risk counseling of some patients.

Endophthalmitis rates among patients receiving intravitreal anti-VEGF injections: a USA claims analysis

Purpose Intravitreal (IVT) injections of the anti-vascular endothelial growth factor (VEGF) agents aflibercept, bevacizumab, and ranibizumab are commonly prescribed to treat neovascular age-related macular degeneration (nAMD). Studies comparing inflammation rates in large populations of patients receiving these agents and the treatment of ocular inflammation post-IVT anti-VEGF injections are scarce. In this study, we compared rates of endophthalmitis claims (sterile and infectious) following IVT anti-VEGF injections to determine the risk factors associated with developing endophthalmitis, and examined the claims for subsequent treatment. Patients and methods This retrospective cohort study of USA claims data examined the risk of developing endophthalmitis following IVT injection of aflibercept, bevacizumab, or ranibizumab in patients with nAMD between 11/18/2011 and 5/31/2013. The primary study outcome was occurrence of endophthalmitis within 30 days of a claim for an IVT anti-VEGF injection. Endophthalmitis rates were calculated separately for aflibercept, bevacizumab, and ranibizumab, followed by pairwise comparisons of endophthalmitis frequencies among the 3 treatments. Results This analysis included 818,558 injections from 156,594 patients with nAMD. The rates (% [n/N]) of endophthalmitis following aflibercept, bevacizumab, and ranibizumab IVT injections were 0.100% (136/135,973), 0.056% (268/481,572), and 0.047% (94/201,013), respectively. In a multivariate analysis, aflibercept was associated with a significantly higher risk of endophthalmitis vs ranibizumab (adjusted odds ratio, 2.19; 95% CI: 1.68–2.85; P<0.0001). The risk of endophthalmitis was similar for bevacizumab and ranibizumab. Within 14 days after endophthalmitis, 38.6% of cases received injectable antibiotics, 15.3% received injectable steroids, and 30.3% underwent vitrectomy. Conclusion The rate of endophthalmitis was very low, but higher following IVT injection with aflibercept compared with both bevacizumab and ranibizumab in patients with nAMD.

Effect of Brimonidine Tartrate 0.15% on Scotopic Pupil: Controlled Trial. V.M. Gerente, A.C. Biondi, C.P. Barbosa, C.L. Lottenberg and A. Paranhos, Jr. J. Ocul. Pharmacol. Ther 2007;23:476–480

To the Editor: We read with interest the article by Gerente and colleagues1 regarding the effect of a single dose of brimonidine tartrate 0.15% on the pupil dark response (pupil dilation in reduced illumination). Although this study confirmed our findings2 that the instillation of brimonidine significantly reduced the dark response in the treated eye, and to a lesser degree, in the untreated eye, we are concerned about the validity of the pupil measurements. The average age of the subjects in this study was 25 years. The mean baseline pupil diameter (PD) was 5.15 mm in the study eye and 5.11 mm in the fellow eye; 8 hours after treatment, it was 4.01 mm (decrease, 1.14) and 4.56 mm (decrease, 0.55), respectively. The PD was measured under so-called “scotopic conditions” at 0.05 lux, using an infrared pupillometer (Eyetec Pupillometer; Sao Carlos, Brazil). The investigators did not report a dark-adaptation protocol, and nothing was mentioned about controlling accommodation. Given the well-established relationship between PD and age, we can predict one from the other: A patient cohort with a mean dark-adapted PD of 5.1 mm should have a mean age of about 60 years, not 25 years, as was reported.3,4 Conversely, we would expect a cohort with a mean age of 25 years to have a mean dark-adapted PD of about 7 mm. This significant measurement error was likely owing to inadequate dark adaptation. Though efforts were made, we were unable to locate any additional information about the Eyetec Pupillometer. Pupil diameter is controlled by the level of rodphotoreceptor activation.5 True dark adaptation under stable environmental illumination, without exposure to stray light sources, is essential to achieve steady-state photoreceptor function. The term “scotopic” refers to a condition of retinal dark adaptation in which cones are entirely quiescent and rods are fully active; it is not defined by, nor directly correlated with, the level of ambient illumination. The persistent misuse of “scotopic conditions” to mean a particular light level has led unwary investigators, editors, and readers to neglect the concept of time-dependent rhodopsin regeneration. In our own research on the pupil dark response, we used a minimum of 5 min of low-light adaptation to achieve a steady-state PD6; we consistently observed a rapid immediate increase in PD, followed by a continued dilation of up to 1 mm over 2–5 min. After a full rod adaptation, the PD became very sensitive to small changes in accommodative tone and exposure to point light sources, such as “on” indicator lights, or even dim reflected light from the shirt or jacket of the examiner moving in front of the patient. These must all be controlled for accurate testing. Although this study provides valuable information about the duration of the antimydriatic effect of a single dose of brimonidine tartrate, readers