Cost-utility Analysis of Opportunistic and Systematic Diabetic Retinopathy Screening Strategies from the Perspective of the Brazilian Public Healthcare System.

OBJECTIVE: To perform a cost-utility analysis of diabetic retinopathy (DR) screening strategies from the perspective of the Brazilian Public Healthcare System. METHODS: A model-based economic evaluation was performed to estimate the incremental costs per quality-adjusted life-year (QALY) gained between three DR screening strategies: (1) the opportunistic ophthalmology referral-based (usual practice), (2) the systematic ophthalmology referral-based, and (3) the systematic teleophthalmology-based. The target population included individuals with type 2 diabetes (T2D) aged 40 years, without retinopathy, followed over a 40-year time horizon. A Markov model was developed with five health states and a 1-year cycle. Model parameters were based on literature and country databases. One-way and probabilistic sensitivity analyses were performed to assess model parameters' uncertainty. WHO willingness-to-pay (WHO-WTP) thresholds were used as reference (i.e. one and three times the Brazilian per capita Gross Domestic Product of R$32747 in 2018). RESULTS: Compared to usual practice, the systematic teleophthalmology-based screening was associated with an incremental cost of R$21445/QALY gained ($9792/QALY gained). The systematic ophthalmology referral-based screening was more expensive (incremental costs = R$4) and less effective (incremental QALY = -0.012) compared to the systematic teleophthalmology-based screening. The probability of systematic teleophthalmology-based screening being cost-effective compared to usual practice was 0.46 and 0.67 at the minimum and the maximum WHO-WTP thresholds, respectively. CONCLUSION: Systematic teleophthalmology-based DR screening for the Brazilian population with T2D would be considered very cost effective compared to the opportunistic ophthalmology referral-based screening according to the WHO-WTP threshold. However, there is still a considerable amount of uncertainty around the results.

Transplantation of conjunctival epithelial cells cultivated ex vivo in patients with total limbal stem cell deficiency.

PURPOSE: To report the outcomes of transplantation of autologous conjunctival epithelial cells cultivated ex vivo (EVCAU) in patients with total limbal stem cell deficiency (LSCD). METHODS: EVCAU were cultivated on denuded human amniotic membrane and transplanted in 12 eyes of 10 patients with total LSCD. We evaluated the improvement in the defined clinical parameters of LSCD (loss of corneal epithelial transparency, superficial corneal neovascularization and epithelial irregularity/recurrent epithelial breakdown), vision acuity, impression cytology, immunocytochemical analysis (CK3/CK19), and the appearance of a regular hexagonal basal layer of cells on corneal confocal microscopy. Histologic and immunohistochemical features were studied in 3 corneal buttons of patients submitted to penetrating keratoplasty after EVCAU. RESULTS: Cultivated conjunctival epithelium formed 4 to 5 layers with the formation of basement membrane-like structures. Immunocytochemical analysis showed positivity for CK3, CK19, MUC5AC, Ki-67, P63, and ABCG2. The improvement of the clinical parameters for this treatment in our cohort was 10 of 12 (83.3%) in a mean follow-up time of 18.5 months (range, 15-26 months), and these eyes showed an improvement in impression cytology, immunocytochemistry, and in vivo confocal analysis. Corneal buttons showed a well-formed epithelium with 5 to 6 layers, with rare cells periodic acid-Schiff+, and positivity for CK3, CK19, P63, connexin 43, and MUC5AC. CONCLUSION: We demonstrated the preliminary results of transplantation of EVCAU for corneal surface reconstruction in cases with total LSCD. Future studies are needed to further assess the long-term efficacy of this procedure.

The role of visual evoked potential and electroretinography in the preoperative assessment of osteo-keratoprosthesis or osteo-odonto-keratoprosthesis surgery.

PURPOSE: To determine the value of electroretinography (ERG) and visual evoked potential (VEP) in predicting visual outcome in patients undergoing osteo-keratoprosthesis (OKP) or osteo-odonto-keratoprosthesis (OOKP) surgery. METHODS: We performed a retrospective cohort study of 143 eyes in 101 patients who underwent OKP or OOKP surgery. The subjects underwent ERG, VEP testing or both up to 6 months prior to surgery. The ERG and VEP results were classified into four categories based on wave amplitude, latency and configuration. The main outcome was the maximum best-corrected visual acuity (maxBCVA) reached at any time postoperatively. RESULTS: One hundred thirty-four cases had undergone preoperative ERG, 82 VEP and 73 both examinations. The sensitivities of ERG and VEP to detect maxBCVA≥0.05 were 68.5% and 87%, respectively, while the specificity was 63.2% for ERG and 47.4% for VEP. The maxBCVA was significantly better in patients with normal ERG (p=0.033) and those with normal VEP (p=0.048), once having defined appropriate normal and abnormal cut-off levels. When comparing fellow eyes in patients who underwent surgery in both eyes, maxBCVA was better in the eyes that had better VEP results (p=0.013). CONCLUSION: Eyes demonstrating normal ERG or VEP achieved better visual outcome than those with abnormal results. In addition, VEP proved instrumental in determining the eye with the best prognosis when comparing both eyes of a given patient.

Clinical utility of objective tests for dry eye disease: variability over time and implications for clinical trials and disease management.

PURPOSE: To evaluate the efficacy of commonly used biomarkers in dry eye disease management in a longitudinal observational case series study followed by an interventional study in a subset of subjects treated with cyclosporine A (0.05%). METHODS: Bilateral tear osmolarity, Schirmer, tear film breakup time (TBUT), staining, meibomian grading, and Ocular Surface Disease Index were measured for a period of 3 consecutive months in participants recruited from a clinic-based population at 2 study sites. Fifty-two subjects completed the study (n = 16 mild/moderate, n = 36 severe; age, 47.1 ± 16.1 years). After the 3-month observation period, severe dry eye patients were prescribed topical cyclosporine A and evaluated for an additional 3 months. RESULTS: Tear osmolarity (8.7 ± 6.3%) exhibited significantly less variability over a 3-month period than corneal staining (12.2 ± 8.8%, P = 0.040), conjunctival staining (14.8 ± 8.9%, P = 0.002), and meibomian grading (14.3 ± 8.8%, P < 0.0001) across the entire patient population. Osmolarity also demonstrated less variation than TBUT (11.7 ± 9.0%, P = 0.059), Schirmer tests (10.7 ± 9.2%, P = 0.67), and Ocular Surface Disease Index (9.3 ± 7.8%, P = 0.94), although the differences were not significant. Variation in osmolarity was less for mild dry eye patients (5.9 ± 3.1%) than severe dry eye patients (10.0 ± 6.9%, P = 0.038). After treatment, average osmolarity and variability were lowered from 341 ± 18 mOsm/L to 307 ± 8 mOsm/L (P < 0.0001, n = 10). A downward trend in symptoms followed changes in osmolarity, declining from 44 ± 17 mOsm/L to 38 ± 18 mOsm/L (P = 0.35). None of the other signs demonstrated a change after treatment. CONCLUSIONS: Over a 3-month period, tear film osmolarity was found to have the lowest variability among commonly used signs of dry eye disease. Reductions in osmolarity preceded changes in symptoms during therapy.