Dark-adapted pupil diameter as a function of age measured with the NeurOptics pupillometer.

PURPOSE: To measure the dark-adapted pupil diameter of normal research participants in their second through ninth decades of life using the NeurOptics pupillometer (Neuroptics Inc). METHODS: Individuals aged 18 to 80 years with no history of eye disease or injury, intraocular surgery, or use of systemic antihistamines or opiates were recruited. After 2 minutes of adaptation at 1 lux illumination, the right dark-adapted pupil diameter was measured using the NeurOptics pupillometer, with accommodation controlled by distance fixation. The NeurOptics pupillometer reported a mean dark-adapted pupil diameter and a standard deviation of the mean, which were analyzed as a function of age-decade. RESULTS: Two-hundred sixty-three individuals participated. For participants aged 18 to 19 years (n=6), the mean dark-adapted pupil diameter was 6.85 mm (range: 5.6 to 7.5 mm); 20 to 29 years (n=66), 7.33 mm (range: 5.7 to 8.8 mm); 30 to 39 years (n=50), 6.64 mm (range: 5.3 to 8.7 mm); 40 to 49 years (n=51), 6.15 mm (range: 4.5 to 8.2 mm); 50 to 59 years (n=50), 5.77 mm (range: 4.4 to 7.2 mm); 60 to 69 years (n=30), 5.58 mm (range: 3.5 to 7.5 mm); 70 to 79 years (n=6), 5.17 mm (range: 4.6 to 6.0 mm); and 80 years (n=4), 4.85 mm (range: 4.1 to 5.3 mm). These values were consistent with studies using infrared photography. The standard deviation was >0.1 mm in 10 (3.8%) participants, all of whom were younger than 55 years. CONCLUSIONS: The dark-adapted pupil diameter is an important clinical variable when planning refractive surgery. Surgeons can compare a patient's dark-adapted pupil diameter with the results of this population study to identify outlier measurements, which may be erroneous, and repeat testing prior to surgery.

A profile on the FoundationFocus CDxBRCA tests.

Introduction: Poly(ADP-ribose) polymerase (PARP) inhibitors, including rucaparib, are the only targeted class of therapeutics approved for recurrent epithelial ovarian carcinoma with a predictive biomarker. Currently, three different PARP inhibitors are approved for either the treatment of ovarian cancer or maintenance of remission following chemotherapy. The Foundation Focus CDxBRCA is an FDA-cleared next-generation sequencing tumor tissue assay that detects somatic and sometimes germline mutations in BRCA1 and BRCA2 genes.Areas covered: The authors discuss the evolution of the ovarian cancer genomic testing landscape relative to PARP inhibition, with a focus on Foundation Focus CDxBRCA and CDxBRCA Loss of Heterozygosity (LOH), the complementary diagnostics (CDx) to rucaparib.Expert opinion: Relatively early in PARP inhibitor development, women with somatic and/or germline mutations in the BRCA1 and BRCA2 genes were found to have higher response rates to PARP inhibitors with longer durability than women who were BRCA wildtype. Other measures of homologous recombination deficiency including LOH have proven to be predictive biomarkers also. Because PARP biomarkers are genomic and complex, co-development of high-performance companion diagnostics was a high priority. The Foundation Focus test began as a next-generation sequencing assay capable of detecting germline (gBRCA) and somatic (sBRCA) mutations that predict response to rucaparib treatment. The addition of LOH to the assay was validated by a clinical trial supporting expansion of the Rucaparib FDA label to include maintenance of chemotherapy response.

Five-year outcomes of intravitreal drug therapy for neovascular age-related macular degeneration in eyes with baseline vision 20/60 or better.

OBJECTIVE: To assess outcomes in treatment-naive eyes with neovascular age-related macular degeneration (nAMD) and good baseline visual acuity (VA) treated using a treat-and-extend (T&E) regimen with intravitreal aflibercept, ranibizumab, or bevacizumab. DESIGN: Single center, retrospective, observational case series. PARTICIPANTS: Ninety-one patients (93 eyes) with nAMD and baseline VA ≥20/60 followed for ≥1 year after the first intravitreal injection. Minimum of 6 (first year) and 3 (subsequent years) and maximum of 12 injections per 12 calendar months. INTERVENTION: Intravitreal aflibercept 2.0 mg, ranibizumab 0.5 mg, or bevacizumab 1.25 mg. Three monthly injections. Treatment interval extended in 2-week increments after resolution of macular edema and reduced in 2-week increments if edema recurred; maximum interval of 12 weeks. Medication changed if edema recurred during and persisted after three monthly injections of original agent. MAIN OUTCOME MEASURES: VA maintenance over time. Total number of injections received by year of treatment. RESULTS: Ninety-three eyes were analyzed. Pretreatment VA was 20/20-20/25 (N=16), 20/30-20/40 (N=47), and 20/50-20/60 (N=30). Mean follow-up was 3.2 years. Follow-up by year was 93, 73, 65, 44, and 26 eyes for years 1-5, respectively. Mean number of injections during years 1-5 was 7.9, 5.9, 5.6, 5.9, and 6.0, respectively; mode number of injections was 7, 5, 3, 6, and 4, respectively. For years 1-5, percent of all eyes at or above baseline was 70%, 66%, 65%, 59%, and 58%, respectively; percent ≥20/60 was 86%, 88%, 86%, 84%, and 77% for years 1-5. For eyes with baseline VA ≥20/40, percent of eyes at or above baseline was 83%, 82%, 81%, 68% and 76% for years 1-5, respectively. CONCLUSION: Using a T&E intravitreal injection protocol, more than 75% of treatment-naive eyes with nAMD and baseline VA ≥20/60 can maintain VA ≥20/60 over 5 years.

The effective corneal refractive surface as a function of a point in visual space: a three-dimensional analysis.

PURPOSE: To develop a three-dimensional optical model of the anterior segment which will provide a basis for understanding the effects of corneal and adnexal problems on vision. METHODS: A three-dimensional optical model of the anterior segment was developed to calculate the effective corneal refractive surface (ECRS), which is a specific area of cornea that refracts incident light rays arising from an object in visual space through the physical pupil (PP); light rays refracted by cornea outside the ECRS do not traverse the PP. This model incorporated the patient variables of central anterior chamber depth (A) and central corneal curvature (K). A vector analysis was combined with three-dimensional analytic geometry to create a unified solution for all object locations in visual space. A computer program in BASIC on a PC was developed to perform the calculations. RESULTS: The ECRS was circular for objects on the line of sight, but with increasing displacement from the fixation point it became oval and eventually crescent shaped. The size of the ECRS increased as the distance of the object from the eye increased, but it rapidly reached a limiting value at about 200 mm. The size of the ECRS increased with PP diameter, but showed only a small dependence on A and minimal dependence on K. CONCLUSION: This comprehensive optical model of object space and the anterior segment of the eye allows clinicians to better understand the effects of corneal light transmission on vision.

Effective corneal refractive diameter as a function of the object tangent angle in visual space.

PURPOSE: To determine whether the currently accepted method of selecting a minimum optical zone diameter for laser refractive surgery that is equal to or slightly greater than the dark-adapted pupil diameter provides a sufficient diameter of corneal surface to focus light arising from objects in the paracentral and peripheral visual field. SETTING: Department of Ophthalmology and Visual Sciences, Texas Tech University Health Sciences Center, Lubbock, Texas, USA. METHODS: An optical model of the anterior segment was developed to calculate the effective corneal refractive diameter (ECRD), which is the diameter of the area of cornea that refracts all incident light rays arising from an object through the physical pupil (PP). This model incorporates the patient variables of central anterior chamber depth (ACD), central corneal curvature (K(c)), and the diameter of the apparent entrance pupil (EP). The model was expanded to incorporate distant objects off the line of sight (LOS), described by their angular displacement from the fixation object in visual space (the object tangent angle delta(ob)). Results were calculated for the 360 meridian degree visual field (ie, for all objects in visual space perceptually displaced from the fixation object by angle delta(ob)). The effect of the prolate nature of the cornea was also investigated. RESULTS: The ECRD expanded rapidly as a function of PP and delta(ob) but was minimally influenced by K(c). Beyond a critical object tangent angle delta(c), light rays striking the corneal vertex were not refracted through the PP, and the ECRD became an annular surface centered on the corneal vertex. The delta(c) was not a function of K, but increased as the PP increased and decreased as the ACD increased. The prolate nature of the cornea had little influence on the ECRD, even for very peripheral light rays. CONCLUSIONS: The ECRD expands rapidly when considering distant objects only slightly displaced from the LOS. A patient treated with an optical zone equal to or slightly greater than the dark-adapted pupil diameter may experience vision quality loss for paracentral and midperipheral objects even under conditions of ambient indoor lighting.

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.

Visual field changes after laser in situ keratomileusis.

PURPOSE: To determine whether laser in situ keratomileusis (LASIK) affects the central 30-degree visual field. SETTING: University-based ophthalmology practice. METHODS: This nonrandomized clinical trial comprised 14 normal patients (27 eyes) scheduled to have LASIK for myopia or myopic astigmatism. Automated static perimetry was performed before and 6 months after surgery using the Octopus 1-2-3 perimeter and the Dynamic-32 test strategy. Patient data included sex, age, preoperative and postoperative refractive errors, preoperative and postoperative best corrected visual acuity, preoperative corneal thickness, programmed optical zone, programmed total ablation diameter, and duration of microkeratome suction. All surgery was performed using the same Alcon LADARVision 4000 excimer laser. The main outcome measures were the mean sensitivity (MS) change in the central 15-degree visual field and the MS change in the 15- to 30-degree visual field. A multivariate analysis of the MS change as a function of preoperative clinical parameters was performed. RESULTS: There was no significant change in the MS in the central 15-degree visual field; between 15 and 30 degrees, there was a statistically significant decrease of -0.82 dB +/- 1.40 (SD) (P=.01, 2-tailed t test). The decline in MS was positively correlated with refractive error and corneal thickness; it was negatively correlated with the programmed optical zone diameter. CONCLUSIONS: Automatic static perimetry can detect decreased sensitivity in the midperipheral visual field after myopic LASIK. It may be a useful quantitative subjective test for measuring the effects of future improvements in surgical technique on vision quality.

Comparison of Colvard pupillometer and infrared digital photography for measurement of the dark-adapted pupil diameter.

PURPOSE: To investigate the accuracy of pupil diameter measurement using the Colvard pupillometer and to determine the learning curve for inexperienced examiners. SETTING: Texas Tech University Health Sciences Center, Lubbock, Texas, USA. METHODS: In this population study, subjects with normal pupillary behavior were tested by 1 of 2 investigators (examiner A, examiner B). After 5 minutes of dark adaptation at 1 lux, digital infrared pupil photography of the right eye was performed, followed by measurement of the horizontal pupil diameter and vertical pupil diameter with the Colvard pupillometer. The photographs were digitally analyzed to determine the horizontal and vertical pupil diameters. During phase I of the study, examiners were masked to the results of infrared pupil photography; during phase II, they reviewed the infrared pupil photography results after each testing session. Bland-Altman plots were created to detect measurement bias; results were graphed by subject test sequence to assess learning. A test difference of less than +/-0.5 mm was considered clinically acceptable. RESULTS: Fifty-nine subjects were tested in phase I, of whom 39 had adequate infrared pupil photography for analysis; 40 were tested in phase II, of whom 34 were included. The mean age of the analyzed subjects was 27 years (range 18 to 44 years). For all subjects, the infrared pupil photography median horizontal pupil diameter was 7.09 mm +/- 0.75 (SD) (range 5.44 to 8.79 mm); the median vertical pupil diameter was 7.22 +/- 0.79 mm (range 5.45 to 9.10 mm). Examiner A initially had a negative bias (Colvard pupillometer value less than infrared pupil photography value) for both horizontal and vertical pupil diameter measurements, which resolved during phase I after 23 subjects were tested; 18 of the final 19 subjects tested (11 phase I, 8 phase II) showed a test difference of less than 0.5 mm for all readings. The pupil diameter did not affect the bias. Examiner B had a strong positive bias that persisted throughout the study. Testing 26 subjects in 5 sessions during phase II did not improve the accuracy. During the final testing session, 3 of 8 subjects had a test difference of 0.5 mm or more in at least 1 dimension. The pupil diameter did not affect the bias. CONCLUSION: The Colvard pupillometer is susceptible to user errors causing unidirectional bias and seems to have a steep and variable learning curve.

Novel MSH2 Mutation in the First Report of a Vietnamese-American Kindred with Lynch Syndrome.

•First report of Lynch syndrome in a Vietnamese kindred•A novel MSH2 mutation has been identified.•Culturally sensitive screening programs need to be developed in this growing population.

Bilateral retinal hemorrhages in an 18-year-old woman.

A previously healthy 18-year-old woman presented with sudden onset of central blurred vision in the right eye. Fundoscopic examination showed retinal venous tortuosity, several flame-shaped hemorrhages bilaterally, and a subhyaloid hemorrhage in the right fovea. Laboratory evaluation and subsequent bone marrow biopsy were consistent with the diagnosis of acute lymphoblastic leukemia. The retinal findings had cleared almost completely by three weeks after initiation of chemotherapy.

Rapid, painless unilateral vision loss in a 37-year-old healthy woman.

A 37-year-old woman experienced painless, progressive vision loss to no light perception in the left eye over the course of 3 days. The right eye was unaffected. On examination, the only other abnormal finding was a +4 left afferent pupillary defect. She was initially diagnosed with retrobulbar optic neuritis and admitted for treatment with intravenous methylprednisolone. Neuro-imaging revealed a large right anterior cerebral artery aneurysm that crossed the midline to compress the left optic nerve. The aneurysm was treated with coil embolization, which was technically successful but which did not lead to significant improvement in vision.

The effect of daily use of brimonidine tartrate on the dark-adapted pupil diameter.

PURPOSE: To investigate the effect of daily brimonidine tartrate 0.15% on the dark-adapted pupil diameter. DESIGN: Observational case series. METHOD: Ten normal volunteers administered brimonidine to their right eyes once daily. Four to six hours later, infrared pupil photographs were taken after dark adaptation. Measurements were performed at baseline; on treatment days 1, 5, 11, and 18; and on washout days 1 and 2. RESULTS: One subject had no response. The nine responding subjects showed an average maximum antimydriatic effect of -1.63 mm (range, -0.57 mm--2.30 mm); all subjects experienced tachyphylaxis. Five subjects showed rebound mydriasis (mean maximum rebound +0.87 mm larger than baseline; range 0.50 mm-1.22 mm). The untreated pupil also responded, showing antimydriasis (two subjects), rebound mydriasis (two subjects), or paradoxical direct mydriasis (one subject). CONCLUSIONS: Once-daily use of brimonidine tartrate to prevent dark-induced pupil dilation can lead to tachyphylaxis and rebound mydriasis.

Iatrogenic ring scotoma after laser in situ keratomileusis.

A 37-year-old ophthalmologist had bilateral simultaneous laser in situ keratomileusis (LASIK) for moderate myopia with astigmatism using the Alcon Summit LADARVision laser; an ablation zone of 5.5 mm was used. Five months after surgery, the uncorrected visual acuity was 20/20 and 20/25 but despite regular corneal topographies, the patient experienced prominent ghost images under photopic and scotopic conditions. To elucidate the nature of the problem, automated static perimetry was performed, which revealed a significant depression between 10 degrees and 30 degrees compared with a baseline study obtained 3 years earlier. The patient started brimonidine 0.2% 1 drop in both eyes every morning, which caused 1.5 to 2.0 mm of pupillary miosis (tonic pupil size 3.0 to 4.0 mm in dim light) and eradicated the ghost images. Repeat perimetry showed significant improvement in all indices. The mechanism of improvement is unclear but may be due to elimination of light scatter from the transition zone between the ablated and unablated cornea. The issue of perimetric changes after refractive surgery deserves more attention; postoperative testing may be indicated for patients in whom the ablation zone diameter is close to the mesopic or scotopic pupil size to provide an accurate lifetime baseline visual field.

Systematic underablation in laser in situ keratomileusis: ablation pattern identified by advanced topographical analysis.

Topographical analysis based on the differential geometry of surfaces-curvature topography-was developed and applied to a patient after laser in situ keratomileusis. The patient had a minimal residual refractive error and normal best corrected visual acuity but had multiple visual aberrations, including ghosting and glare, unless the pupils were maximally constricted. The corneal loci responsible for the aberrations were difficult or impossible to identify on axial topographies but were readily identified with curvature topography. The patient's ablations appeared to be miniature versions of the intended ablation profiles, with small areas of emmetropic central cornea surrounded by annuli of rapidly increasing keratometric power; that is, systematic underablation. This may explain why some patients have visual aberrations with pupil diameters smaller than the programmed optical zones.