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Thomas J, Armstrong G. Use of Yamane technique for secondary intraocular lens implantation following open globe injury. BMJ Case Rep 2023;16(11)Abstract
A woman in her 50s presented with suspected open globe injury (OGI) of the right eye after being hit with a high velocity piece of plastic. Visual acuity at the time of presentation was counting fingers in the affected eye. Slit lamp examination revealed a full thickness laceration of the cornea and a traumatic cataract. Primary corneal repair was performed and the patient was left aphakic after cataract removal. Secondary intraocular lens placement was deferred for 2 years, after which time a scleral-fixated intraocular lens was implanted using the Yamane technique. Postoperative visual acuity of 20/50 was achieved, with the vision limited by persistent diabetic macular oedema. Thus, this case of successful implantation of a secondary lens using the Yamane technique in a patient with prior corneal laceration and traumatic cataract highlights that the Yamane technique can result in visual improvement in patients with prior OGI.
Avilés EC, Wang SK, Patel S, Shi S, Lin L, Kefalov VJ, Goodrich LV, Cepko CL, Xue Y. High temporal frequency light response in mouse retina is mediated by ON and OFF bipolar cells and requires FAT3 signaling. bioRxiv 2023;Abstract
Vision is initiated by the reception of light by photoreceptors and subsequent processing via parallel retinal circuits. Proper circuit organization depends on the multi-functional tissue polarity protein FAT3, which is required for amacrine cell connectivity and retinal lamination. Here we investigated the retinal function of Fat3 mutant mice and found decreases in physiological and perceptual responses to high frequency flashes. These defects did not correlate with abnormal amacrine cell wiring, pointing instead to a role in bipolar cell subtypes that also express FAT3. Indeed, similar deficits were observed in mice lacking the bipolar cell glutamate receptors GRIK1 (OFF-bipolar cells) and GRM6 (ON-bipolar cells). Mechanistically, FAT3 binds to the synaptic protein PTPσ and is required to localize GRIK1 to OFF-cone bipolar cell synapses with cone photoreceptors. How FAT3 impacts ON-cone bipolar cell function at high temporal frequency remains to be uncovered. These findings expand the repertoire of FAT3's functions and reveal the importance of both ON- and OFF-bipolar cells for high frequency light response.
Sun JA, Yuan M, Johnson GE, Pasquale LR, Boland MV, Friedman DS, Elze T, Shen LQ, Wang M. Comparison of Structural and Functional Features in Primary Angle-Closure and Open-Angle Glaucomas. J Glaucoma 2023;Abstract
PRECIS: Using a large dataset, we showed structural and functional differences between primary angle closure glaucoma and primary open angle glaucoma. Primary angle closure glaucoma has relative structural preservation and worse functional loss inferiorly. PURPOSE: To identify structural and functional differences in primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG). PATIENTS AND METHODS: In this large cross-sectional study, differences in structural and functional damage were assessed among POAG and PACG patients with optical coherence tomography and reliable visual field testing. RESULTS: 283 PACG and 4,110 POAG patients were included. Despite similar mean deviation on visual fields (mean [standard deviation] -7.73 [7.92] vs. -7.53 [6.90] dB, P=0.72), PACG patients had thicker global retinal nerve fiber layer (RNFL), smaller cup volume, smaller cup-to-disc ratio, and larger rim area than POAG (77 [20] vs. 71 [14] µm, 0.32 [0.28] vs. 0.40 [0.29] mm3, 0.6 [0.2] vs. 0.7 [0.1], 1.07 [0.40] vs. 0.89 [0.30] mm2, P<0.001 for all), while POAG patients had more pronounced inferior RNFL thinning (82 [24] vs. 95 [35] µm, P<0.001). In a multivariable analysis, hyperopia (odds ratio (OR): 1.24, confidence interval (CI): 1.13-1.37), smaller cup-to-disc ratio (OR: 0.69, CI: 0.61-0.78), thicker inferior RNFL (OR: 1.15, CI: 1.06-1.26) and worse mean deviation (OR: 0.95, CI: 0.92-0.98) were associated with PACG. Functionally, POAG was associated with superior paracentral loss and PACG with inferior field loss. After adjusting for average RNFL thickness, PACG was associated with more diffuse loss than POAG (TD differences 1.26-3.2 dB). CONCLUSIONS: PACG patients had less structural damage than POAG patients despite similar degrees of functional loss. Regional differences in patterns of functional and structural loss between POAG and PACG may improve disease monitoring for these glaucoma subtypes.
Shi M, Sun JA, Lokhande A, Tian Y, Luo Y, Elze T, Shen LQ, Wang M. Artifact Correction in Retinal Nerve Fiber Layer Thickness Maps Using Deep Learning and Its Clinical Utility in Glaucoma. Transl Vis Sci Technol 2023;12(11):12.Abstract
PURPOSE: Correcting retinal nerve fiber layer thickness (RNFLT) artifacts in glaucoma with deep learning and evaluate its clinical usefulness. METHODS: We included 24,257 patients with optical coherence tomography and reliable visual field (VF) measurements within 30 days and 3,233 patients with reliable VF series of at least five measurements over ≥4 years. The artifacts are defined as RNFLT less than the known floor value of 50 µm. We selected 27,319 high-quality RNFLT maps with an artifact ratio (AR) of <2% as the ground truth. We created pseudo-artifacts from 21,722 low-quality RNFLT maps with AR of >5% and superimposed them on high-quality RNFLT maps to predict the artifact-free ground truth. We evaluated the impact of artifact correction on the structure-function relationship and progression forecasting. RESULTS: The mean absolute error and Pearson correlation of the artifact correction were 9.89 µm and 0.90 (P < 0.001), respectively. Artifact correction improved R2 for VF prediction in RNFLT maps with AR of >10% and AR of >20% up to 0.03 and 0.04 (P < 0.001), respectively. Artifact correction improved (P < 0.05) the AUC for progression prediction in RNFLT maps with AR of ≤10%, >10%, and >20%: (1) total deviation pointwise progression: 0.68 to 0.69, 0.62 to 0.63, and 0.62 to 0.64; and (2) mean deviation fast progression: 0.67 to 0.68, 0.54 to 0.60, and 0.45 to 0.56. CONCLUSIONS: Artifact correction for RNFLTs improves VF and progression prediction in glaucoma. TRANSLATIONAL RELEVANCE: Our model improves clinical usability of RNFLT maps with artifacts.
Gharahkhani P, He W, Han X, Ong JS, Rentería ME, Wiggs JL, Khawaja AP, Trzaskowski M, Mackey DA, Craig JE, Hewitt AW, Hewitt AW, Macgregor S, Wu Y. Genome-wide risk prediction of primary open-angle glaucoma across multiple ancestries. medRxiv 2023;Abstract
BACKGROUND: Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. The disease is often only diagnosed after retinal ganglion cell damage has occurred, with current treatments unable to restore lost vision. Developing risk identification tools for POAG will help enable timely diagnosis and prevent irreparable damage from occurring, especially for ancestry groups (such as African (AFR)) where the disease prevalence is high. Given the heritable nature of POAG, we aim to develop a polygenic score (PGS), which could facilitate earlier POAG risk detection for timely prevention and diagnosis. METHODS: We applied a multi-ancestry multi-trait approach to build powerful PGS for POAG. We first integrated the new and existing genetics data on POAG and two key endophenotypes, intraocular pressure (IOP) and vertical cup-to-disc ratio (VCDR). We then leveraged the shared POAG genetic information across European (EUR), AFR and Asian ancestries and between POAG and each of IOP and VCDR to develop PGS for POAG risk prediction. We systematically assessed the PGS prediction power and risk stratification ability in POAG cohorts of different ancestries. RESULTS: Our newly developed PGS showed improved accuracy compared to previous PGS for POAG risk prediction in EUR ancestry. We showed the transferability of PGS based on EUR ancestry in the prediction of POAG status in AFR and Asian ancestries. Utilizing the shared genetic information across ancestries further improved PGS prediction power for POAG in AFR and East Asian (EAS). For individuals with South Asian ancestry, those in the top PGS decile were diagnosed ~18 years earlier than those in the bottom decile. For AFR ancestry, individuals in the top percentile had an odds ratio of 4.08 (95% CI: 2.33-7.45) compared with the remainder of the population using the newly developed AFR-specific PGS. CONCLUSIONS: In the current study, we developed PGS for POAG risk prediction in EUR, Asian and AFR populations. These PGS, to our best knowledge, are the most powerful PGS currently for POAG risk screening and stratification. We believe that our study will lead to improved POAG detection across diverse populations in the future by enabling targeting clinical screening of people at high levels of genetic risk.
Dean J, McTavish S, Feng Y, Hoyek S, Patel NA. Persistent Inflammation Associated With HLA-B27 After Pars Plana Vitrectomy With Scleral Buckle Placement. J Vitreoretin Dis 2023;7(6):557-561.Abstract
Purpose: To report 2 cases of persistent inflammation associated with human leukocyte antigen-B27 (HLA-B27) after pars plana vitrectomy (PPV) with scleral buckling. Methods: Two cases were analyzed. Results: A 47-year-old man had pars plana vitrectomy (PPV), scleral buckle (SB) placement, and endolaser for a macula-on rhegmatogenous retinal detachment (RRD). A 61-year-old man also had uneventful PPV, SB placement, and endolaser for a macula-off RRD. Postoperatively, both patients reported eye pain and had persistent intraocular inflammation. Both were found to be HLA-B27 positive despite having no previous signs or symptoms that would warrant HLA-B27 testing. Conclusions: Discovering the source of prolonged postoperative inflammation is critical in initiating the correct treatment and removing suspicion of infection. Although intraocular inflammation associated with HLA-B27 does not often present initially after surgery, HLA-B27 testing should be considered in cases of persistent, unexpected postoperative inflammation.
Holmes S, Reyes N, Huang JJ, Galor A, Pattany PM, Felix ER, Moulton EA. Disentangling the neurological basis of chronic ocular pain using clinical, self-report, and brain imaging data: use of K-means clustering to explore patient phenotypes. Front Neurol 2023;14:1265082.Abstract
INTRODUCTION: The factors that mediate the expression of ocular pain and the mechanisms that promote chronic ocular pain symptoms are poorly understood. Central nervous system involvement has been postulated based on observations of pain out of proportion to nociceptive stimuli in some individuals. This investigation focused on understanding functional connectivity between brain regions implicated in chronic pain in persons reporting ocular pain symptoms. METHODS: We recruited a total of 53 persons divided into two cohorts: persons who reported no ocular pain, and persons who reported chronic ocular pain, irrespective of ocular surface findings. We performed a resting state fMRI investigation that was focused on subcortical brain structures including the trigeminal nucleus and performed a brief battery of ophthalmological examinations. RESULTS: Persons in the pain cohort reported higher levels of pain symptoms relating to neuropathic pain and ocular surface disease, as well as more abnormal tear metrics (stability and tear production). Functional connectivity analysis between groups evinced multiple connections exemplifying both increases and decreases in connectivity including regions such as the trigeminal nucleus, amygdala, and sub-regions of the thalamus. Exploratory analysis of the pain cohort integrating clinical and brain function metrics highlighted subpopulations that showed unique phenotypes providing insight into pain mechanisms. DISCUSSION: Study findings support centralized involvement in those reporting ocular-based pain and allude to mechanisms through which pain treatment services may be directed in future research.
, Berry JL, Pike S, Rajagopalan A, Reid MW, Fabian ID, Afshar AR, Alejos A, Alemany-Rubio E, Alfonso Carreras Y, Arazi M, Astbury NJ, Bascaran C, Binkley E, Blum S, Boldt CH, Bonanomi MTBC, Bowman R, Brennan RC, Burton MJ, Calderón-Sotelo P, Jara DCA, Cano MR, Castillo L, Cavieres I, Cerna DQ, Chandramohan A, Chantada GL, Corson TW, Cowan-Lyn KE, Davanzo JM, Demirci H, Coronado RDY, Dimaras H, Macedo CDR, Ericksen C, Fandiño AC, Fernández DDPG, Foster A, Fu LD, Fuentes-Alabi SL, Garcia JL, Pacheco HGN, Girón AV, Goenz MA, Gold AS, Gomel N, Gonzalez E, Gonzalez Perez G, González-Rodríguez L, Graells J, Grigorovski NDAK, Hamel P, Hansen ED, Harbour WJ, Elizabeth Hartnett M, Hassan M, Hubbard BG, Kapelushnik N, Kim JW, Larson SA, Laurenti KD, Leverant AA, Li C, López JP, Luna-Fineman S, Magrath GN, Mallipatna A, Mattosinho CCDS, Mets MB, Miller A, Mruthyunjaya P, Murray TG, Oliver SCN, Oporto J, Ortega-Hernández M, Ossandon D, Morales CPR, Paton KE, Plager DA, Polania RA, Ponce J, Quintero D K, Ramasubramanian A, Ramirez-Ortiz MA, Randhawa JK, Romero L, Salas B, Sánchez GL, Orozco AJS, Sgroi M, Shah AS, Shields CL, Singh AD, Skalet AH, Stacey AW, Stahl ED, Strahlendorf C, Suarez MEC, Superstein R, Leiva FTF, Teixeira LF, Uner OE, Anchaya JKV, Vaughan LO, Villegas VM, Wilson MW, Yaghy A, Yee RI, López AM, Zondervan M. Retinoblastoma Outcomes in the Americas: a prospective analysis of 491 children with retinoblastoma from 23 American countries. Am J Ophthalmol 2023;Abstract
PURPOSE: Globally, disparities exist in retinoblastoma treatment outcomes between high- and low-income countries, but independent analysis of American countries is lacking. We report outcomes of American retinoblastoma patients and explore factors associated with survival and globe salvage. DESIGN: Subanalysis of prospective cohort study data. METHODS: Multicenter analysis at 57 American treatment centers in 23 countries of varying economic levels (low income=LIC, lower-middle=LMIC, upper-middle=UMIC, high=HIC) of 491 treatment-naïve retinoblastoma patients diagnosed in 2017 and followed through 2020. Survival and globe salvage rates analyzed with Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: Of patients, 8 (1.6%), 58 (11.8%), 235 (47.9%) and 190 (38.7%) were from LIC, LMIC, UMIC and HIC, respectively. Three-year survival rates in LICs were 60.0% (95% CI, 12.6-88.2) compared to 99.2% (94.6-99.9) in HICs. Death was less likely in patients older than four years (vs. four or younger, HR=0.45 [95% CI, 0.27 - 0.78], P=0.048). Patients with more advanced tumors (e.g., cT3 vs. cT1, HR= 4.65 × 109 [95% CI, 1.25 × 109 - 1.72 × 1010], P<0.001) and females (vs. males, HR=1.98 [1.27-3.10], P=0.04) were more likely to die. Three-year globe salvage rates were 13.3% (95% CI, 5.1-25.6) in LMICs and 46.2% (38.8-53.3) in HICs. At three years, 70.1% of cT1 eyes (95% CI, 54.5-81.2) versus 8.9% of cT3 eyes (5.5-13.3) were salvaged. Advanced tumor stage was associated with higher enucleation risk (e.g., cT3 vs. cT1, SHR=4.98 [95% CI, 2.36-10.5), P<0.001). CONCLUSIONS: Disparities exist in survival and globe salvage in American countries based on economic level and tumor stage demonstrating a need for childhood cancer programs.
Micheletti S, Galli J, Vezzoli M, Scaglioni V, Agostini S, Calza S, Merabet LB, Fazzi E. Academic skills in children with cerebral palsy and specific learning disorders. Dev Med Child Neurol 2023;Abstract
AIM: To investigate the prevalence and clinical manifestations of reading, writing, and mathematics disorders in children with cerebral palsy (CP). We explored how the clinical profile of these children differed from those with specific learning disorders (SLDs), taking into account several factors, particularly IQ scores, neuropsychological aspects, and the presence of a visual impairment. METHOD: A prospective cross-sectional study was conducted in 42 children with CP (mean age 9 years 8 months; SD = 2 years 2 months) and 60 children with SLDs (mean age 10 years; SD = 1 year 7 months). Clinical characteristics, neuromotor and cognitive profiles, neuropsychological aspects (speech performance, academic skills, visual attention, phonological awareness, working memory), and signs of visual impairment (visual acuity, contrast sensitivity, visual field, oculomotor functions) were assessed. A machine learning approach consisting of a random forest algorithm, where the outcome was the diagnosis and the covariates were the clinical variables collected in the sample, was used for the analyses. RESULTS: About 59% of the children with CP had reading, writing, or mathematics disorders. Children with CP with learning disorders had a low performance IQ, normal phonological awareness, and working memory difficulties, whereas children with SLDs had normal performance IQ, impaired phonological awareness, and mild working memory difficulties. There were no differences in verbal IQ between the two groups. INTERPRETATION: Learning disorders are frequently associated with CP, with different clinical characteristics, compared with SLDs. Assessment of academic skills is mandatory in these children, even if the IQ is normal. At school age, specific interventions to promote academic skills in children with CP could be a major rehabilitative goal.
Romano F, Lamanna F, Boon CJF, Siligato A, Kalra G, Agarwal A, Medori C, Bertelli M, Pellegrini M, Invernizzi A, Staurenghi G, Salvetti AP. Clinical, Genotypic and Imaging Characterization of the spectrum of ABCA4 Retinopathies. Ophthalmol Retina 2023;Abstract
PURPOSE: To investigate the clinical and genotypic differences in the spectrum of ABCA4-associated retinopathies (ABCA4R). DESIGN: Observational, cross-sectional case series. PARTICIPANTS: Sixty-six patients (132 eyes) carrying biallelic ABCA4 variants. METHODS: Patients underwent visual acuity measurement and multimodal imaging. Clinical records were reviewed for age at onset, presenting symptoms, genetic variants, and electroretinogram (ERG). Each eye was assigned to a phenotype based on age at onset, imaging and ERG: cone dystrophy-bull's eye maculopathy (CD-BEM, 40 eyes), cone-rod dystrophy (CRD, 12 eyes), Stargardt disease (SD, 28 eyes), late-onset SD (LO-SD, 38 eyes), fundus flavimaculatus (FFM, 14 eyes). Images were analyzed for: peripapillary sparing, retinal pigment epithelium (RPE) atrophy (definitely decreased autofluorescence, DDAF), flecks patterns using autofluorescence; type of atrophy according to CAM reports, macular and choroidal thickness on optical coherence tomography (OCT); choriocapillaris flow deficits on OCT angiography. MAIN OUTCOME MEASURES: Primary outcome was to report the demographic, genotypic and imaging characteristics of the different ABCA4R phenotypes. Secondary objectives included the assessment of imaging biomarkers as outcome measures for clinical trials. RESULTS: Age at onset was lower in CRD (12±8 years) and higher in LO-SD patients (59±9 years) (all p<0.01). Central vision loss was a common presenting symptom in CD-BEM and SD, whereas LO-SD patients primarily complained of difficult dark adaptation. Missense variants were more frequent in CD-BEM, and splice site in CRD and LO-SD (p<0.05). Peripapillary sparing was absent in three eyes with LO-SD (8%). CD-BEM eyes typically had cORA alterations (98%), while CRD and SD eyes showed both cORA and cRORA (71-100%). LO-SD patients had larger areas of DDAF (100% cRORA) and of choriocapillaris flow deficits (all p<0.01). Repeatability of DDAF measurements was low for some phenotypes (CD-BEM and CRD) and atrophic areas <7.5 mm2. Resorbed flecks were significantly associated with CRD and LO-SD (p<0.01). CONCLUSIONS: This research provides a thorough evaluation of the spectrum of ABCA4R. Our findings suggest that certain phenotypes show preferential photoreceptor degeneration (e.g., CD-BEM), while others have substantial RPE and choriocapillaris alterations (e.g., LO-SD). We recommend that clinical trial endpoints take into consideration these imaging features to improve the interpretation of their results.
Aiello LP, Jacoba CMP, Ashraf M, Cavallerano JD, Tolson AM, Tolls D, Sun JK, Silva PS. INTEGRATING MACULAR OPTICAL COHERENCE TOMOGRAPHY WITH ULTRAWIDE-FIELD IMAGING IN A DIABETIC RETINOPATHY TELEMEDICINE PROGRAM USING A SINGLE DEVICE. Retina 2023;43(11):1928-1935.Abstract
PURPOSE: To determine the effect of combined macular spectral-domain optical coherence tomography (SD-OCT) and ultrawide field retinal imaging (UWFI) within a telemedicine program. METHODS: Comparative cohort study of consecutive patients with both UWFI and SD-OCT. Ultrawide field retinal imaging and SD-OOCT were independently evaluated for diabetic macular edema (DME) and nondiabetic macular abnormality. Sensitivity and specificity were calculated with SD-OCT as the gold standard. RESULTS: Four hundred twenty-two eyes from 211 diabetic patients were evaluated. Diabetic macular edema severity by UWFI was as follows: no DME 93.4%, noncenter involved DME (nonciDME) 5.1%, ciDME 0.7%, ungradable DME 0.7%. SD-OCT was ungradable in 0.5%. Macular abnormality was identified in 34 (8.1%) eyes by UWFI and in 44 (10.4%) eyes by SD-OCT. Diabetic macular edema represented only 38.6% of referable macular abnormality identified by SD-OCT imaging. Sensitivity/specificity of UWFI compared with SD-OCT was 59%/96% for DME and 33%/99% for ciDME. Sensitivity/specificity of UWFI compared with SDOCT was 3%/98% for epiretinal membrane. CONCLUSION: Addition of SD-OCT increased the identification of macular abnormality by 29.4%. More than 58.3% of the eyes believed to have any DME on UWF imaging alone were false-positives by SD-OCT. The integration of SD-OCT with UWFI markedly increased detection and reduced false-positive assessments of DME and macular abnormality in a teleophthalmology program.
Kamat V, Grumbine MK, Bao K, Mokate K, Khalil G, Cook D, Clearwater B, Hirst R, Harman J, Boeck M, Fu Z, Smith LEH, Goswami M, Wubben TJ, Walker EM, Zhu J, Soleimanpour SA, Scarlett JM, Robbings BM, Hass D, Hurley JB, Sweet IR. A versatile pumpless multi-channel fluidics system for maintenance and real-time functional assessment of tissue and cells. Cell Rep Methods 2023;3(11):100642.Abstract
To address the needs of the life sciences community and the pharmaceutical industry in pre-clinical drug development to both maintain and continuously assess tissue metabolism and function with simple and rapid systems, we improved on the initial BaroFuse to develop it into a fully functional, pumpless, scalable multi-channel fluidics instrument that continuously measures changes in oxygen consumption and other endpoints in response to test compounds. We and several other laboratories assessed it with a wide range of tissue types including retina, pancreatic islets, liver, and hypothalamus with both aqueous and gaseous test compounds. The setup time was less than an hour for all collaborating groups, and there was close agreement between data obtained from the different laboratories. This easy-to-use system reliably generates real-time metabolic and functional data from tissue and cells in response to test compounds that will address a critical need in basic and applied research.
Mujat M, Sampani K, Patel AH, Sun JK, Iftimia N. Cellular-Level Analysis of Retinal Blood Vessel Walls Based on Phase Gradient Images. Diagnostics (Basel) 2023;13(22)Abstract
Diseases such as diabetes affect the retinal vasculature and the health of the neural retina, leading to vision problems. We describe here an imaging method and analysis procedure that enables characterization of the retinal vessel walls with cellular-level resolution, potentially providing markers for eye diseases. Adaptive optics scanning laser ophthalmoscopy is used with a modified detection scheme to include four simultaneous offset aperture channels. The magnitude of the phase gradient derived from these offset images is used to visualize the structural characteristics of the vessels. The average standard deviation image provides motion contrast and enables segmentation of the vessel lumen. Segmentation of blood vessel walls provides quantitative measures of geometrical characteristics of the vessel walls, including vessel and lumen diameters, wall thickness, and wall-to-lumen ratio. Retinal diseases may affect the structural integrity of the vessel walls, their elasticity, their permeability, and their geometrical characteristics. The ability to measure these changes is valuable for understanding the vascular effects of retinal diseases, monitoring disease progression, and drug testing. In addition, loss of structural integrity of the blood vessel wall may result in microaneurysms, a hallmark lesion of diabetic retinopathy, which may rupture or leak and further create vision impairment. Early identification of such structural abnormalities may open new treatment avenues for disease management and vision preservation. Functional testing of retinal circuitry through high-resolution measurement of vasodilation as a response to controlled light stimulation of the retina (neurovascular coupling) is another application of our method and can provide an unbiased evaluation of one's vision and enable early detection of retinal diseases and monitoring treatment results.
Singh RB, Parmar UPS, Jhanji V. Prevalence and economic burden of Keratoconus in the United States. Am J Ophthalmol 2023;Abstract
PURPOSE: To assess the prevalence and economic burden of Keratoconus in the United States. DESIGN: Retrospective cohort study to estimate prevalence and economic burden. METHODS: Patients enrolled in Medicaid and Children's Health Insurance Program (CHIP) who were diagnosed with keratoconus between 2016 and 2019 were included. The data reported to the Centers for Disease Control and Prevention (CDC) Vision and Eye Health Surveillance System (VEHSS) was analyzed. The crude prevalence rates (national and state-wise) were obtained from the database and extrapolated to estimate the keratoconus case count in the United States. The keratoconus prevalence was compared between males and females was compared using Mann-Whitney test, whereas Brown Forsythe one-way analysis of variance test was used to compare prevalence between age and racial groups. Furthermore, Dunnett's T3 multiple comparison test for intergroup comparison. Finally, the economic burden of keratoconus was assessed by inflation adjusted direct costs to patients and total cases in the country. RESULTS: In the cohort of 69,502,000 patients enrolled for Medicaid and CHIP, the national prevalence of keratoconus was computed to be 0.04% in 2019 and has increased from 0.03% in 2016. The highest prevalence of keratoconus is observed in patients aged 18 to 39 years, followed by 40 to 64 years; however comparable prevalence rates were observed in these age groups in Black population. The prevalence was moderately higher in females compared to males; however significantly higher keratoconus prevalence was observed in Black females compared to males. A significantly high prevalence of keratoconus was observed in Black population followed by Hispanic population. In 2019, the average inflation adjusted lifetime cost of keratoconus treatment was USD 28,766.69 with a cumulative economic burden of USD 3.8 billion. CONCLUSIONS: Keratoconus is most prevalent in 18-39-year-olds individuals. Keratoconus prevalence is higher in Black population, specifically females and the diagnosis is often delayed in these patients.

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