Autoimmune Inflammatory Eye Disease: Demystifying Clinical Presentations for the Internist.

PURPOSE OF REVIEW: Provide a framework for recognizing key symptoms and clinical findings in patients with autoimmune inflammatory eye disease. RECENT FINDINGS: The most common manifestations of autoimmune inflammatory eye disease are episcleritis, scleritis, uveitis (anterior, intermediate, posterior, and panuveitis), and keratoconjunctivitis sicca. Etiologies can be idiopathic or in association with a systemic autoimmune condition. Referral of patients who may have scleritis is critical for patients presenting with red eyes. Referral of patients who may have uveitis is critical for patients presenting often with floaters and vision complaints. Attention should also be directed to aspects of the history that might suggest a diagnosis of a systemic autoimmune condition, immunosuppression, drug-induced uveitis, or the possibility of a masquerade condition. Infectious etiologies should be ruled out in all cases. Patients with autoimmune inflammatory eye disease may present with ocular or systemic symptoms alone, or in combination. Collaboration with ophthalmologists and other relevant specialists is vital to optimal long-term medical care.

0.18 MG FLUOCINOLONE ACETONIDE INSERT FOR THE TREATMENT OF CHRONIC POSTOPERATIVE PSEUDOPHAKIC CYSTOID MACULAR EDEMA.

PURPOSE: To report the outcomes of the 0.18 mg fluocinolone acetonide insert (FAi) in the treatment of chronic (>6 months) postoperative cystoid macular edema after cataract surgery. METHODS: This was a retrospective consecutive case series of eyes with chronic postoperative cystoid macular edema treated with the FAi. Visual acuity, intraocular pressure, optical coherence tomography metrics, and supplemental therapies were extracted from the charts before and at 3, 6, 12, 18, and 21 months after FAi placement, when available. RESULTS: Nineteen eyes of 13 patients with chronic postoperative cystoid macular edema after cataract surgery underwent FAi placement with an average follow-up of 15.4 months. Ten eyes (52.6%) had a ≥2-line gain in visual acuity. Sixteen eyes (84.2%) had a ≥20% reduction in optical coherence tomography central subfield thickness. Eight eyes (42.1%) had complete resolution of CME. Improvements in central subfield thickness and visual acuity were sustained throughout individual follow-up. Compared with 18 eyes (94.7%) requiring local corticosteroid supplementation before FAi, only six eyes (31.6%) required supplementation after FAi. Similarly, of the 12 eyes (63.2%) that were on corticosteroid drops before FAi, only 3 (15.8%) required drops after FAi. CONCLUSION: Eyes with chronic postoperative cystoid macular edema after cataract surgery treated with the FAi had improved and sustained visual acuity and optical coherence tomography metrics, along with a reduction in supplemental treatment burden.

Artificial intelligence in dementia.

PURPOSE OF REVIEW: Artificial intelligence tools are being rapidly integrated into clinical environments and may soon be incorporated into dementia diagnostic paradigms. A comprehensive review of emerging trends will allow physicians and other healthcare providers to better anticipate and understand these powerful tools. RECENT FINDINGS: Machine learning models that utilize cerebral biomarkers are demonstrably effective for dementia identification and prediction; however, cerebral biomarkers are relatively expensive and not widely available. As eye images harbor several ophthalmic biomarkers that mirror the state of the brain and can be clinically observed with routine imaging, eye-based machine learning models are an emerging area, with efficacy comparable with cerebral-based machine learning models. Emerging machine learning architectures like recurrent, convolutional, and partially pretrained neural networks have proven to be promising frontiers for feature extraction and classification with ocular biomarkers. SUMMARY: Machine learning models that can accurately distinguish those with symptomatic Alzheimer's dementia from those with mild cognitive impairment and normal cognition as well as predict progressive disease using relatively inexpensive and accessible ocular imaging inputs are impactful tools for the diagnosis and risk stratification of Alzheimer's dementia continuum. If these machine learning models can be incorporated into clinical care, they may simplify diagnostic efforts. Recent advancements in ocular-based machine learning efforts are promising steps forward.

CLINICAL CHARACTERISTICS AND VISUAL OUTCOMES IN ENDOPHTHALMITIS AFTER KERATOPROSTHESIS IMPLANTATION.

PURPOSE: To describe the presentation, microbiology, management, and prognosis of eyes with endophthalmitis after Boston keratoprosthesis implantation. METHODS: Retrospective case series with history, diagnostics, management, and outcomes data in endophthalmitis after keratoprosthesis implantation presenting to a tertiary center between 2009 and 2020. RESULTS: Of 137 keratoprosthesis-implanted eyes, 7 eyes of 7 patients (5%) developed endophthalmitis. On presentation, 6 (86%) reported decreased visual acuity, and only 1 (14%) reported pain. Peripheral corneal ulcers were present in 2 eyes (29%). Seidel testing was negative in all cases. Six eyes (86%) had retroprosthetic membranes. One (14%) underwent initial pars plana vitrectomy with mechanical vitreous biopsy, whereas 6 (86%) received a needle vitreous tap-half of which were dry. Organisms were isolated after vitreous tap in two eyes: Streptococcus intermedius and Mycobacterium abscessus. The mean visual acuity preendophthalmitis, at presentation, and at 6 months were 20/267, 20/5,944, and 20/734, respectively. The visual acuity improved 9.08 ± 11.78 Early Treatment Diabetic Retinopathy Study lines from presentation to 6 months. Six-month visual acuity was correlated with preendophthalmitis visual acuity (r = 0.92, P = 0.003) but not presenting visual acuity (P = 0.838). CONCLUSION: Visual acuity at 6 months is correlated with preendophthalmitis visual acuity, not presenting visual acuity. Endophthalmitis should be considered in the differential diagnosis of painless intraocular inflammation any time after keratoprosthesis implantation, even if Seidel negative.

ASSESSMENT OF RETINAL MICROVASCULAR ALTERATIONS IN INDIVIDUALS WITH AMNESTIC AND NONAMNESTIC MILD COGNITIVE IMPAIRMENT USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To assess retinal microvascular alterations in individuals with amnestic mild cognitive impairment (MCI) and nonamnestic MCI. METHODS: One hundred twelve eyes of 59 amnestic MCI participants, 32 eyes of 17 nonamnestic MCI participants, and 111 eyes of 56 controls with normal cognition were included. Optical coherence tomography angiography vessel density and perfusion density in the Early Treatment Diabetic Retinopathy Study 3-mm circle and ring were assessed. Retinal thickness parameters including retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, central subfield thickness, and subfoveal choroidal thickness were also analyzed. Multivariable generalized estimating equations were used for statistical analysis. RESULTS: Perfusion density in the 3-mm inner ring was significantly lower in amnestic MCI patients when compared with nonamnestic MCI participants (0.29 ± 0.03 vs. 0.34 ± 0.09, P = 0.025) and controls with normal cognition (0.29 ± 0.03 vs. 0.39 ± 0.02, P < 0.001), after adjustment for age and sex as covariates. Vessel density, retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, central subfield thickness, and subfoveal choroidal thickness did not differ among or between diagnostic groups. CONCLUSION: Perfusion density was significantly reduced in individuals with amnestic MCI, compared with those with nonamnestic MCI and controls with normal cognition.

LONGITUDINAL FOLLOW-UP OF TUBERCULAR SERPIGINOUS-LIKE CHOROIDITIS USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To analyze and describe serial follow-up of choriocapillaris alterations in tubercular serpiginouslike choroiditis (SLC) using optical coherence tomography angiography (OCTA) and to compare it with multimodal imaging. METHODS: In this prospective cohort study, patients with active tubercular SLC underwent OCTA using Optovue RTVue XR Avanti and other imaging techniques including enhanced-depth imaging OCT (EDI-OCT) (Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany), fundus autofluorescence, fluorescein angiography, and indocyanine green angiography. Serial imaging was performed for a total follow-up of 3 months. Choriocapillaris alterations at the site of lesions were analyzed on OCTA imaging, and their mean lesion areas were calculated. RESULTS: Twenty-six eyes (26 patients; 20 males; mean age: 32.68 ± 10.56 years) were included. Fourteen eyes had active multifocal lesions (n = 39), whereas 12 eyes had active placoid lesions (n = 12). At baseline, OCTA showed hyporeflective flow deficit lesions corresponding to the hypofluorescent lesions on indocyanine green angiography in all eyes. In the multifocal type of SLC, the mean lesion area decreased in all eyes compared with baseline, and lesions with a lesion area less than 0.1 mm2 on OCTA showed near-complete resolution with minimal choriocapillaris atrophy. In comparison, all eyes with a placoid type of SLC showed no significant reduction in the lesion area and showed extensive choriocapillaris atrophy. CONCLUSION: Optical coherence tomography angiography has the unique ability to demonstrate pathological flow impairment at the level of choriocapillaris in active tubercular SLC. Serial OCTA analysis reveals that large tubercular SLC lesions result in choriocapillaris atrophy as the lesions heal, whereas smaller multifocal lesions show resolution of choriocapillaris hypoperfusion with minimal atrophy.

Time to disease recurrence in noninfectious uveitis following long-acting injectable fluocinolone acetonide implant.

PURPOSE: To determine the time to disease recurrence with long-acting injectable fluocinolone acetonide implant (FAi) for noninfectious intermediate, posterior, and panuveitis. METHODS: This was a retrospective study of patients with at least 12 months of follow-up who had completed a 2-year prospective, investigational new drug study with 0.18-mg FAi. Time to uveitis recurrence or cystoid macular edema (CME) occurrence was recorded. RESULTS: Twelve eyes from 12 participants (mean age 43 years, range 25-64 years) were included. Patients were followed for a mean of 34.2 months (range, 12.0-56.9 months) after completion of the prospective trial. Five eyes (42%) did not have a documented uveitis recurrence or CME occurrence. Five eyes (42%) had a uveitis recurrence with the mean time to recurrence 36.1 months (range, 22.8-61.1 months) after FAi implantation. Two eyes (16%) had CME alone, the mean time to occurrence 36.9 months (range 36.1-42.1 months). On Kaplan-Meier analysis, the estimated probability of remaining recurrence-free 36 months after FAi implantation was 0.67 (95% confidence interval, 0.34-0.86). CONCLUSIONS: Data of study participants after completing a clinical trial suggest that the injectable FAi for noninfectious uveitis can provide control for 3 years on average. These long-term data support the use of FAi to control noninfectious uveitis.

Appearance of pediatric choroidal neovascular membranes on optical coherence tomography angiography.

PURPOSE: Compared with fluorescein angiography (FA), the gold standard for diagnosing choroidal neovascularization (CNV) activity, optical coherence tomography angiography (OCTA) is non-invasive without risks associated with fluorescein dye use, and may be especially advantageous in the diagnosis and monitoring of children with CNV. METHODS: Eight eyes from eight patients aged 12 months to 18 years were imaged with the investigational Spectralis OCTA (version 6.9, Heidelberg Engineering, Heidelberg, Germany) and the RTVue XR Avanti (Optovue Inc., Fremont, CA, USA). Two patients were imaged during examination under anesthesia while six patients were imaged in the clinic. Demographic information, ocular characteristics, treatment history, and imaging studies (color photos, fluorescein angiography, OCT) were collected and reviewed. RESULTS: Three eyes had active CNV while five had quiescent CNV at the time of imaging. CNV was idiopathic or secondary to trauma, retinal vascular dysgenesis versus retinopathy of prematurity, pigmentary retinopathy, Best vitelliform macular dystrophy, panuveitis, morning glory disc anomaly, and optic disc drusen. OCTA of two active CNV demonstrated presence of a main trunk with multiple fine capillaries, vessel loops, and anastomoses. OCTA was repeated after treatment for two CNV and demonstrated a decrease in size with loss of fine capillaries, vessel loops, and anastomoses. For the third active CNV, OCTA verified flow in the CNV complex despite the uncertainty of FA hyperfluorescence in the setting of grossly abnormal retinal vasculature. The five quiescent CNV all lacked fine capillaries, vessel loops, and anastomoses on OCTA. CONCLUSION: OCTA demonstrates morphological differences between active and quiescent pediatric CNV.

AUTOLOGOUS RETINAL TRANSPLANTATION AS A PRIMARY TREATMENT FOR LARGE CHRONIC MACULAR HOLES.

PURPOSE: To report the outcomes of autologous neurosensory retinal transplant as a primary treatment for patients with large chronic macular holes and evaluate the safety and feasibility of the procedure. DESIGN: Retrospective study, consecutive case series. METHODS: We reviewed seven patients with a primary chronic large macular hole, who underwent autologous neurosensory retinal transplant. Mean preoperative minimum and maximum hole diameters were 643 µm and 1214 µm, respectively. Changes in visual acuity were measured postsurgery, and optical coherence tomography, fluorescein angiography, and microperimetry-3 were analyzed after the procedure. RESULTS: Closure of the macular hole was achieved in all seven eyes in the study. At 1 year post-surgery, there was significant improvement in mean visual acuity (LogMAR 1.10 vs. 0.68, P = 0.001). Optical coherence tomography showed that all grafts had formed attachments to the retinal epithelial cells of the recipient retina. Mean preoperative ellipsoid zone defect was 1,089 ± 403.8 µm (range, 918-1,329 µm) which further decreased to 921 ± 129.1 µm (range, 670-1,201 µm) at final follow up (P = 0.09). Microperimetry-3 testing indicated retinal sensitivity in the graft in five eyes. CONCLUSION: Autologous retinal transplantation may help rebuild the macular structure resulting in functional improvement for eyes with primary chronic large macular hole.

Use of Letermovir as Salvage Therapy for Drug-Resistant Cytomegalovirus Retinitis.

Treatment options for drug-resistant cytomegalovirus (CMV) are limited. Letermovir is a novel antiviral recently approved for CMV prophylaxis following hematopoietic cell transplantation, but its efficacy in other settings is unknown. We recently used letermovir for salvage treatment in four solid organ transplant recipients with ganciclovir-resistant CMV retinitis. All patients improved clinically without known adverse drug events. However, three patients failed to maintain virologic suppression, including two patients who developed genotypically confirmed resistance to letermovir while on therapy.

Autologous Retinal Transplant for Refractory Macular Holes: Multicenter International Collaborative Study Group.

PURPOSE: To report the structural and functional outcomes of autologous neurosensory retinal transplant for closure of refractory large macular holes (MHs). DESIGN: Multicenter, retrospective, consecutive case series. PARTICIPANTS: A total of 41 eyes of 41 patients with a full-thickness MH refractory to prior vitrectomy with internal limiting membrane (ILM) peel and tamponade. METHODS: All patients underwent pars plana vitrectomy, autologous neurosensory retinal transplant with gas, silicone oil tamponade, or short-term perfluoro-n-octane heavy-liquid tamponade. All patients had at least 6 months' follow-up. MAIN OUTCOME MEASURES: Anatomic closure of MH, change in ellipsoid zone (EZ) and external limiting membrane (ELM) defect on OCT, visual acuity (VA) recovery, and surgical complications were analyzed. RESULTS: Mean number of prior surgeries was 1.5±0.94 (range, 1-3), and patients were followed for a mean of 11.1±7.7 months (range, 6-36 months). Complete anatomic closure of MH by OCT was achieved in 36 of 41 eyes (87.8%). Mean corrected VA (logarithm of the minimum angle of resolution [logMAR]) improved (P = 0.03) from 1.11±0.66 (range, 0.48-3) to 1.03±0.51 (range, 0.1-2) at the last postoperative visit. The VA improved (≥0.3 logMAR units) in 15 eyes (36.6%), was stable in 17 eyes (41.5%), and worsened in 9 eyes (21.9%). Among eyes with anatomic closure, VA improved in 52.3% and worsened in 13.8%, whereas in those without closure, VA worsened in 40% and improved in none. Mean preoperative largest basal diameter was 1468.1±656.4 µm (range, 621-2600 µm), and mean inner-opening diameter was 825±422.5 µm (range, 336-1649 µm). Mean preoperative EZ defect was 1777.3±513.8 µm (range, 963-2808 µm), which decreased to 1370±556.9 µm (range, 288-2000 µm) at final follow-up (P = 0.007). Mean preoperative ELM was 1681.5±429 µm (range, 1172-2606 µm), which decreased to 1408.5±571.2 µm (range, 200-2000 µm) at final follow-up (P = 0.017). Major postoperative complications were retinal detachment (n = 1) and vitreous hemorrhage (n = 1). There were no cases of proliferative vitreoretinopathy, endophthalmitis, suprachoroidal hemorrhage, or choroidal neovascularization. CONCLUSIONS: The autologous retinal transplant technique offers a high degree of anatomic success and proved safe in this initial experience for closure of refractory MHs.

The role of cystoid macular edema as a marker in the progression of non-paraneoplastic autoimmune retinopathy.

PURPOSE: To determine the relationship between cystoid macular edema (CME) and disease severity and progression in non-paraneoplastic autoimmune retinopathy (npAIR). METHODS: A retrospective study was conducted on patients seen between 2008 and 2016 with npAIR as defined by electroretinogram (ERG) dysfunction, visual field changes, presence of antiretinal antibodies, a negative malignancy workup, and no other apparent cause for visual dysfunction. Optical coherence tomography (OCT) scans were reviewed for each patient. A minimum follow-up of 1 year was necessary for study inclusion. The presence or absence of CME and the length of the preserved EZ on the centermost line scan of the SD-OCT images was recorded at each visit. The main outcome measure assessed was the rate of EZ loss (EZ final - EZ initial / days follow-up) over time, a marker for disease progression. RESULTS: Thirty-two eyes (16 patients) were included with an average follow-up of 42 months. Twenty-one eyes (66%) had CME on initial presentation and final follow-up (group 1), eight eyes (25%) did not have CME on presentation or final follow-up (group 2), and three eyes (9%) did not have CME on presentation but developed CME during follow-up (group 3). Group 1 eyes had a lower maximal a-wave amplitude (59.0 vs. 220.9 mV, p = 0.012) and lower maximal b-wave amplitude (88.1 vs 256.9 mV, p = 0.017) on baseline ERG compared to Group 2 eyes. The rate of EZ loss over time was significantly greater for group 1 with CME compared to group 2 without CME both at 12 months (- 1.26 µm/day vs. - 0.26 µm/day, p = 0.022) and at final follow-up (- 1.03 µm/day vs. - 0.08 µm/day, p = 0.012). CONCLUSIONS: CME was associated with decreased ERG amplitudes and greater velocity of EZ loss, suggesting that CME is a useful biomarker of more severe and more progressive disease in npAIR.

COMBINED AUTOLOGOUS TRANSPLANTATION OF NEUROSENSORY RETINA, RETINAL PIGMENT EPITHELIUM, AND CHOROID FREE GRAFTS.

PURPOSE: To evaluate the feasibility and initial functional and anatomical outcomes of transplanting a full-thickness free graft of choroid and retinal pigment epithelium (RPE), along with neurosensory retina in advanced fibrosis and atrophy associated with end-stage exudative age-related macular degeneration with and without a concurrent refractory macular hole. METHODS: During vitrectomy, an RPE-choroidal and neurosensory retinal free graft was harvested in nine eyes of nine patients. The RPE-choroidal and neurosensory retinal free graft was either placed subretinally (n = 5), intraretinally to cover the foveal area inside an iatrogenically induced macular hole over the RPE-choroidal graft (n = 3) or preretinally (n = 1) without a retinotomy wherein both free grafts were placed over the concurrent macular hole. Silicone oil endotamponade was used in all cases. RESULTS: Mean follow-up was 7 ± 5.5 months (range 3-19). The mean preoperative visual acuity was ∼count fingers (logarithm of the minimum angle of resolution = 2.11, range 2-3), which improved to ∼20/800 (logarithm of the minimum angle of resolution 1.62 ± 0.48, range 0.7-2, P = 0.04). Vision was stable in 5 eyes (55.6%) and improved in 4 eyes (44.4%). Reading ability improved in 5 eyes (55.6%). Postoperative complications were graft atrophy (n = 1), epiretinal membrane (n = 1), and dislocation of neurosensory retina-choroid-RPE free graft (n = 1). CONCLUSION: Combined autologous RPE-choroid and neurosensory retinal free graft is a potential surgical alternative in eyes with end-stage exudative age-related macular degeneration, including concurrent refractory macular hole.

Femtosecond cataract laser capsulotomy enabling optic capture and secondary sulcus iol insertion in an eye with traumatic aniridia and aphakia.

PURPOSE: To describe a surgical technique and intraoperative modifications to create a secondary capsulotomy using the femtosecond cataract laser in an eye with traumatic aphakia and aniridia. METHODS: The expanded use of the femtosecond cataract laser (Catalys Precision Laser System; Optimedica, Sunnyvale, CA) for creation of a well-centered and circular secondary capsulotomy in the capsular remnants of an eye with traumatic aphakia and aniridia. RESULTS: Using software modifications based on intraoperative anterior segment spectral-domain optical coherence tomography imaging, and customizing the capsulotomy settings, the femtosecond cataract laser was able to penetrate through most of the fused anterior and posterior capsular leaflets and a circular capsulotomy was achieved. The latter permitted optic capture and excellent centration of a three-piece intraocular lens placed in the sulcus with good postoperative visual rehabilitation. CONCLUSION: The femtosecond cataract laser can be customized to create a well-centered and circular secondary capsulotomy in aniridic and aphakic eyes where optic capture is critical for long-term intraocular lens stability.

Autoimmune retinopathy and antiretinal antibodies: a review.

PURPOSE: To review the current state for diagnosis and management of autoimmune retinopathy. METHODS: A review of the literature was performed, encompassing autoimmune retinopathy including paraneoplastic retinopathy (cancer-associated retinopathy, melanoma-associated retinopathy, and bilateral diffuse uveal melanocytic proliferation) and non-paraneoplastic autoimmune retinopathy. Based on this review, current principles and techniques for diagnosis and the treatments reported for autoimmune retinopathy are discussed with the aim to clarify some of the confusion that exists regarding this complex entity. RESULTS: Autoimmune retinopathy encompasses a spectrum of retinal degeneration phenotypes. The clinical features, fundus characteristics, and electroretinogram findings for paraneoplastic and non-paraneoplastic retinopathy are reviewed. The different antiretinal antibodies reported in these entities are described. The diagnostic approaches for detecting these antiretinal antibodies and their limitations are covered. The treatments reported for autoimmune retinopathy and their outcomes are reviewed. CONCLUSION: Among the myriad of antiretinal antibodies reported, challenges persist in determining which antibodies are pathogenic and which are benign and what factors cause antiretinal antibodies to become pathologic. There also remain difficulties in the detection and accurate measurement of antiretinal antibodies, and the response to therapeutic intervention in autoimmune retinopathy is variable.

Evolution of Autoimmune Retinopathy in Stiff Person Syndrome: A Case Report.

PURPOSE: To report a case of autoimmune retinopathy (AIR) as the presenting feature of Stiff Person Syndrome (SPS) and assess its evolution. OBSERVATIONS: A 35-year-old man presented with progressive, chronic, vision loss. On initial examination, visual acuity measured 20/20 OD and 20/50 OS. Humphrey Visual Field testing (HVF) demonstrated decreased foveal threshold OU. Mild subfoveal ellipsoid zone loss was noted on Optical Coherence Tomography (OCT). Five years later the patient presented with painful lower extremity muscle spasms and stiffness and complained of increasing vision loss with difficulty distinguishing colors. OCT showed marked progression of ellipsoid zone loss. Scotoma were demonstrated on HVF and electroretinography demonstrated reduced responses consistent with bilateral severe maculopathy. Serum testing showed autoantibodies to the glutamic acid decarboxylase 65-kilodalton isoform (GAD65) at a high titer and a diagnosis of AIR in the setting of SPS was made. A systemic workup for malignancy was negative. The patient was treated with IVIG and transitioned to rituximab with improvement in systemic symptoms. CONCLUSIONS: and Importance: Unlike previous cases of AIR in the setting of SPS, vision symptoms and OCT changes presented years before the onset of muscle spasms. Etiologies such as SPS should be on the differential of unexplained retinopathy, even in the absence of systemic symptoms, especially when paraneoplastic etiologies are ruled out.

Aqueous and Plasma Levels of Phosphorylated Tau 181 in Individuals with Normal Cognition.

Background: Plasma and cerebrospinal fluid (CSF) levels of p-tau181 have been associated with Alzheimer's disease (AD). The retina and vitreous have shown measurable quantities of phosphorylated tau 181 (p-tau181). The aqueous humor, which can be collected during cataract surgery, may have measurable concentrations of p-tau181. Objective: To determine whether p-tau181 is detectable in the aqueous humor and if so, whether it is associated with other measures that might be consistent with AD such as higher plasma p-tau181 concentration and lower Montreal Cognitive Assessment (MoCA-BLIND version 7.1) score. Methods: Aqueous humor samples, blood samples, and MoCA-BLIND scores were collected from patients who did not carry a clinical diagnosis of cognitive impairment at the time of cataract surgery. Aqueous p-tau181 concentrations and plasma p-tau181 concentrations were then measured using ultra-sensitive single-molecule assay ELISA technology. A rank-transformed mixed-effects multivariate regression model was used to determine associations between aqueous concentrations, plasma concentrations, and MoCA-BLIND scores. Results: 16 eyes of 16 participants were enrolled with an average age of 71.6. Average MoCA-BLIND score was 20.6/22, average aqueous p-tau181 concentration was 6.4 pg/mL, and average plasma p-tau181 concentration was 3.1 pg/mL. Higher plasma p-tau181 was significantly associated with higher aqueous p-tau181 (p = 0.02). Aqueous p-tau181 and plasma p-tau181 were negatively associated with MoCA-BLIND scores (p = 0.005 and p = 0.001 respectively) in these patients. Conclusions: Aqueous p-tau181 is positively correlated with plasma p-tau181 and is negatively correlated with MoCA-BLIND scores. Further study in individuals with mild cognitive impairment or AD characterized by cerebrospinal fluid and volumetric MRI metrics may yield further insights.