Quantitative cone contrast threshold testing in patients with differing pathophysiological mechanisms causing retinal diseases.

BACKGROUND: Cone contrast threshold testing (CCT) provides quantitative measurements of color and contrast function to reveal changes in vision quality that are not standard endpoints in clinical trials. We utilize CCT to measure visual function in patients with multiple sclerosis (MS), age-related macular degeneration (AMD), epiretinal membrane (ERM), and retinal vein occlusion (RVO). METHODS: Retrospective data was gathered from 237 patients of the Gavin Herbert Eye Institute. Subjects included 17 patients with MS, 45 patients with AMD, 41 patients with ERM, 11 patients with RVO, and 123 healthy controls. Patients underwent the primary measurement outcome, CCT testing, as well as Sloan visual acuity test and spectral domain optical coherence tomography during normal care. RESULTS: Color and contrast deficits were present in MS patients regardless of history of optic neuritis. AMD with intermediate or worse disease demonstrated reduced CCT scores. All 3 stages of ERM demonstrated cone contrast deficits. Despite restoration of visual acuity, RVO-affected eyes demonstrated poorer CCT performance than unaffected fellow eyes. CONCLUSIONS: CCT demonstrates color and contrast deficits for multiple retinal diseases with differing pathophysiology. Further prospective studies of CCT in other disease states and with larger samples sizes is warranted.

Risk Factors for Meibomian Gland Disease Assessed by Meibography.

Purpose: To elucidate risk factors for meibomian gland disease (MGD) and understand associated changes in meibography and in relation to ocular surface disease. Patients and Methods: As part of the standard workup for ocular surface disease at a tertiary academic center, 203 patients received an ocular history and lifestyle questionnaire. The questionnaire included detailed inquiries about ocular health and lifestyle, including makeup use, cosmetic eyelid procedures, screen time, and contact lens habits. Subjects also took the standardized patient evaluation of eye dryness (SPEED) II questionnaire. Meibomian gland (MG) dropout and structural changes were evaluated on meibography and scored by three independent graders using meiboscores. Statistical analysis was conducted to identify significant risk factors associated with MG loss. Results: This retrospective, cross-sectional study included 189 patients (378 eyes) with high-quality images for grading, and the average age was 67 years (77% female). Patients older than 45 years had significantly more dropout than younger patients (p < 0.01). Self-reported eye makeup use did not significantly impact MG loss. Patients with a history of blepharoplasty trended toward higher meiboscores, but the difference was not statistically significant. Self-reported screen time did not affect meiboscores. Contact lens use over 20 years was associated with significant MG loss (p < 0.05). SPEED II scores had no relationship to meiboscores (p = 0.75). Conclusion: Older age is a significant risk factor for MG loss. Any contact lens use over 20 years also impacted MG dropout. Highlighting the incongruence of symptoms to signs, SPEED II scores showed no relationship to the structural integrity of MGs.

Seeing invisible light: 2-photon microperimetry to measure visual function.

Purpose: The accuracy of conventional visual function tests, which emit visible light, decreases in patients with corneal scars, cataracts, and vitreous hemorrhages. In contrast, infrared (IR) light exhibits greater tissue penetrance than visible light and is less susceptible to optical opacities. We therefore compared conventional visual function tests against infrared 2-phton microperimetry (2PM-IR) in a subject with a brunescent nuclear sclerotic and posterior subcapsular cataract before and after cataract surgery. Methods: Testing using infrared light microperimetry from a novel device (2PM-IR), visible light microperimetry from a novel device (2PM-Vis), conventional microperimetry, and the cone contrast threshold (CCT) test were performed before and after cataract surgery. Results: Retinal sensitivity assessed using 2PM-IR, 2PM-Vis, and cMP improved by 3.4 dB, 17.4 dB, and 18 dB, respectively. Cone contrast threshold testing improved for the S-cone, M-cone, and l-cone by 111, 14, and 30. Conclusions and Importance: 2PM-IR, unlike conventional visual function tests, showed minimal variability in retinal sensitivity before and after surgery. Thus, IR visual stimulation may provide a more accurate means of measuring neurosensory retinal function by circumventing optical media opacities, aiding in the diagnosis of early macular disease.

Treatment of Choroidal Metastasis from Epidermal Growth Factor Mutant Non-Small Cell Lung Cancer with First-line Osimertinib Therapy.

PURPOSE: To illustrate the regression of a metastatic lesion through ophthalmic imaging and correlating findings with standard chest imaging and treatment with osimertinib, an oral chemotherapy agent specific to Epidermal Growth Factor Receptor + Non-small Cell Lung Cancer (EGFR+ NSCLC). CASE REPORT: A 63-year-old Asian male presented to ophthalmology with a complaint of left blurry vision. Initial ophthalmic exam revealed a choroidal lesion and imaging results highlighted a spiculated lung mass with brain and bony metastases. Osimertinib was chosen for its specificity and ability to cross the blood-brain barrier. Follow-up ophthalmic and radiographic imaging were repeated over the course of treatment. CONCLUSION: After the initiation of osimertinib, ophthalmic and computed tomography imaging highlighted the regression of the ocular metastatic disease and primary malignancy, respectively.Osimertinib is an effective first-line treatment of EGFR+ NSCLC and corresponding metastatic sites. Additionally, ophthalmic imaging can be used to monitor general response to chemotherapy agents when ocular metastasis is identified.

Dupilumab Induced Limbal Stem Cell Deficiency.

Dupilumab is a monoclonal antibody that is used for the treatment of atopic dermatitis (AD) in adults. However, increasing reports of ocular complications including conjunctivitis and dry eye disease have been documented. In this report, we describe a case of a patient who developed limbal stem cell deficiency (LSCD) after prolonged Dupilumab use. A 56-year-old Caucasian male with a history of AD presented with gradual onset cloudy vision and extensive diffuse symblepharon resulting from Dupilumab treatment. He was diagnosed with cicatrizing blepharoconjunctivitis and secondary LSCD after slit lamp examination. In conclusion, LSCD secondary to cicatricial disease is a severe adverse ocular complication caused from long-term Dupilumab treatment.

Two-Photon Microperimetry: A Media Opacity-Independent Retinal Function Assay.

Purpose: Compare results obtained using infrared two-photon microperimetry (2PM-IR) with conventional visual function tests in healthy subjects of varying ages with and without simulated media opacities. Methods: Subjects from two separate cohort studies completed cone contrast threshold (CCT) testing, conventional microperimetry, visible light microperimetry from a novel device (2PM-Vis), and infrared two-photon microperimetry. The first cohort study, which consisted of six healthy volunteers (23 to 29 years of age), evaluated the effects of simulated media opacities on visual performance testing. Subjects underwent testing on four visual function devices nine separate times under the following conditions: no filter, red filter, green filter, blue filter, light brown filter, dark brown filter, polarized black filter (0° rotation), and polarized black filter (90° rotation). Subjects subsequently performed 2PM-IR and 2PM-Vis testing without a filter in the mydriatic state. The second cohort study evaluated the effect of age on visual test performance in 42 healthy subjects split between two groups (ages 20-40 years and 60-80 years). Results: Retinal sensitivity measured by 2PM-IR demonstrated lower variability than all other devices relying on visible spectrum stimuli. Retinal sensitivity decreased proportionally with the transmittance of light through each filter. CCT scores and retinal sensitivity decreased with age in all testing modalities. Visible spectrum testing modalities demonstrated larger test result differences between young and old patient cohorts; this difference was inversely proportional to the wavelength of the visual function test. Conclusions: 2PM-IR mitigates media opacities that may mask small differences in retinal sensitivity when tested with conventional visual function testing devices. Translational Relevance: Conventional visual function tests that emit visible light may not detect differences in retinal function during the early stages of age-related diseases due to the confounding effects of cataracts. Infrared light, which has greater transmittance through ocular tissue, may reliably quantify retinal sensitivity and thereby detect degenerative changes early on.

Quantifying Color Vision Changes Associated With Cataracts Using Cone Contrast Thresholds.

Purpose: To evaluate effects of age and simulated and real cataractous changes on color vision as measured by the high-definition cone contrast test (CCT). Methods: Twenty-four healthy volunteers from two cohort studies performed CCT using best-corrected visual acuity, filters, mydriasis, and pinhole correction. Retrospective cross-sectional study of patients seen in eye clinics evaluated the relationship between age and color vision, and age and lens status in 355 eyes. Last, 25 subjects underwent CCT before and after cataract surgery. Results: CCT scores were most reliable in the nonmydriatic condition without pinhole correction. Progressively dense brown filters produced small decreases in S-cone sensitivity. Linear regression analysis of phakic subjects showed a decline for all cone classes with age. Rate of decline was greater for S-cones (slope = -1.09; 95% confidence interval [CI], -1.30 to 0.86) than M-cones (slope = -0.80; 95% CI, -1.03 to -0.58) and L-cones (slope = -0.66; 95% CI, -0.88 to -0.44). CCT scores increased for S-cones but reduced for L- and M-cones in pseudophakic subjects compared with phakic patients. CCT scores after cataract surgery increased for S-cones, M-cones, and L-cones by 33.0 (95% CI, 8.6 to 57.4), 24.9 (95% CI, 3.8 to 46.0), and 22.0 (95% CI, -3.2 to 47.3), respectively. Conclusions: CCT assessment allows for clinically practical quantitation of color and contrast vision improvement after cataract surgery and aging patients who note poor vision despite good visual acuity. Translational Relevance: CCT testing, which quantifies hereditary and acquired color deficiency, can also quantify the degree of cataract severity and, combined with other parameters, can provide more precise guidance for cataract extraction to optimize patient care.