Publications

2022

Zeng R, Garg I, Bannai D, Kasetty M, Katz R, Park J, Lizano P, Miller J. Retinal microvasculature and vasoreactivity changes in hypertension using optical coherence tomography-angiography. Graefes Arch Clin Exp Ophthalmol. 2022;260(11):3505–3515.
PURPOSE: To evaluate the retinal vasculature and vasoreactivity of patients with hypertension (HTN) using spectral domain optical coherence tomography angiography (SD-OCTA). METHODS: Patients with and without a diagnosis of HTN were included in this cross-sectional observational study. All eyes were imaged with SD-OCTA using 3 mm × 3 mm and 6 mm × 6 mm centered on both the fovea and optic disk. A second 6 mm × 6 mm scan was taken after a 30 s breath-hold. Vessel density (VD), vessel skeletonized density (VSD), and fractal dimension (FD) were calculated using customized MATLAB scripts. Vessel diameter index (VDI) was obtained by taking the ratio of VD to VSD. Vasoreactivity was measured by subtracting the VD or VSD before and after breath-hold (∆VD, ∆VSD). RESULTS: Twenty-three eyes with HTN (17 patients) and 17 control eyes (15 patients) were included. In the 6 mm × 6 mm angiogram centered on fovea, the superficial capillary plexus (SCP) VD (ß =  - 0.029, p = 0.012), VSD (ß =  - 0.004, p = 0.043) and the choriocapillaris VD (ß =  - 0.021, p = 0.030) were significantly decreased in HTN compared to control eyes. Similarly, FD was decreased in both the SCP (ß =  - 0.012, p = 0.013) and choriocapillaris (ß =  - 0.009, p = 0.030). In the 3 mm × 3 mm angiogram centered on optic disk, SCP VDI (ß =  - 0.364, p = 0.034) was decreased. ∆VD and ∆VSD were both reduced in the DCP (ß =  - 0.034, p = 0.032; ß =  - 0.013, p = 0.043) and ∆VSD was elevated in the choriocapillaris of HTN eyes (ß = 0.004, p = 0.032). CONCLUSIONS: The study used SD-OCTA to show significant differences in the retinal vasculature of hypertensive patients. It was also the first to demonstrate the potential of OCT-A to investigate retinal vascular reactivity in patients with HTN.
Kitazawa K, Inotmata T, Shih K, Hughes JW, Bozza N, Tomioka Y, Numa K, Yokoi N, Campisi J, Dana R, Sotozono C. Impact of aging on the pathophysiology of dry eye disease: A systematic review and meta-analysis. Ocul Surf. 2022;25:108–118.
PURPOSE: Dry eye disease (DED) is a common age-related ocular surface disease. However, it is unknown how aging influences the ocular surface microenvironment. This systematic review aims to investigate how the aging process changes the ocular surface microenvironment and impacts the development of DED. METHODS: An article search was performed in PubMed, EMBASE, and Web of Science. 44 studies reporting on age-related ocular changes and 14 large epidemiological studies involving the prevalence of DED were identified. 8 out of 14 epidemiological studies were further analyzed with meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. Study-specific estimates (impact of aging on the prevalence of DED) were combined using one-group meta-analysis in a random-effects model. RESULTS: Meta-analysis revealed the prevalence of DED in the elderly aged 60 years old or older was 5519 of 60107 (9.2%) and the odds ratio of aging compared to younger age was 1.313 (95% confidence interval [CI]; 1.107, 1.557). With increasing age, the integrity of the ocular surface and tear film stability decreased. Various inflammatory cells, including senescent-associated T-cells, infiltrated the ocular surface epithelium, lacrimal gland, and meibomian gland, accompanied by senescence-related changes, including accumulation of 8-OHdG and lipofuscin-like inclusions, increased expression of p53 and apoptosis-related genes, and decreased Ki67 positive cells. CONCLUSIONS: The aging process greatly impacts the ocular surface microenvironment, consequently leading to DED.
Madjedi K, Stuart K, Chua S, Foster P, Strouthidis N, Luben R, Warwick A, Kang J, Wiggs J, Pasquale L, Khawaja A. The Association of Female Reproductive Factors with Glaucoma and Related Traits: A Systematic Review. Ophthalmol Glaucoma. 2022;5(6):628–647.
TOPIC: This systematic review summarizes evidence for associations between female reproductive factors (age at menarche, parity, oral contraceptive [OC] use, age at menopause, and postmenopausal hormone [PMH] use) and intraocular pressure (IOP) or open-angle glaucoma (OAG). CLINICAL RELEVANCE: Understanding the associations between female reproductive factors and glaucoma may shed light on the disease pathogenesis and aid clinical prediction and personalized treatment strategies. Importantly, some factors are modifiable, which may lead to new therapies. METHODS: Two reviewers independently extracted articles in MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases to identify relevant studies. Eligibility criteria included studies with human subjects aged > 18 years; a measured outcome of either IOP or OAG; a cohort, case-control, cross-sectional, or randomized controlled trial design; a reported measure of association, such as the hazard ratio, relative risk, odds ratio, or mean difference, with an associated confidence interval; and a measured exposure of at least 1 of the following variables: age at menarche, parity, OC use, age at menopause, or PMH use. RESULTS: We included a total of 27 studies. Substantial differences in study designs, exposure and treatment levels, treatment durations, and variable reporting precluded a meaningful quantitative synthesis of the identified studies. Overall, relatively consistent associations between PMH use and a lower IOP were identified. Estrogen-only PMH use may be associated with lower OAG risk, which may be modified by race. No significant associations were found with combined estrogen-and-progesterone PMH use. No strong associations between parity or age at menarche and glaucoma were found, but a younger age at menopause was associated with an increased glaucoma risk, and adverse associations were identified with a longer duration of OC use, though no overall association with OC use was found. CONCLUSIONS: The association between PMH use and lower IOP or OAG risk is a potentially clinically relevant and modifiable risk factor and should be investigated further, although this needs to be interpreted in the context of a high risk of bias across included studies. Future research should examine associations with IOP specifically and how the relationship between genetic factors and OAG risks may be influenced by female reproductive factors.
Gaier E, Rasool N, Rizzo J. Sectoral Sparing Associated With a Cilioretinal Artery in Arteritic Anterior Ischemic Optic Neuropathy. J Neuroophthalmol. 2022;42(2):e514-e516.
ABSTRACT: Giant cell arteritis (GCA) is a life-threatening vasculitis occurring in older adults that can cause blindness by ischemia of the choroid, retina, and optic nerve. We report a case of a patient who presented with "occult" GCA with severe anterior ischemic optic neuropathy affecting both optic nerves, delayed choroidal filling, and a concomitant cilioretinal artery occlusion in the left eye. The retinal territory supplied by the affected cilioretinal artery was hypoperfused, yet this retinal territory at least partially corresponded to the only preserved visual field in that eye. The sector of the optic disc corresponding to the emergence of the cilioretinal artery was the only sector spared by pallid edema. This pattern of sectoral sparing associated with a cilioretinal artery has been observed in other patients with GCA and in animal models of posterior ciliary artery occlusion. This case serves as a clear example of an incompletely understood phenomenon in posterior pole circulation in vascular occlusive disease that deserves further study.
Vongsachang H, Bleicher I, Reshef E, Stagner A, Wolkow N. Wells Syndrome Presenting as Atypical Periorbital Cellulitis. Ophthalmic Plast Reconstr Surg. 2022;38(6):e167-e170.
A 62-year-old man presented with diffuse, painless, left-sided preseptal edema, erythema, and woody induration extending to the left temple. The induration generated an orbital compartment syndrome with markedly elevated intraocular pressure necessitating lateral canthotomy and cantholysis. Although atypical for an infectious etiology, empiric broad-spectrum intravenous antibiotics were initiated with no improvement. A tissue biopsy demonstrated extensive perivascular and interstitial eosinophils with focal flame figures, and the patient was diagnosed with a severe hypersensitivity reaction or eosinophilic cellulitis (Wells syndrome). The disease process remitted rapidly upon initiation of oral prednisone. Wells syndrome is a rare inflammatory eosinophilic dermatosis, most often presenting in the limbs and trunk, with few reports of facial and periorbital involvement. This case highlights the importance of considering Wells syndrome in the differential diagnosis of atypical periorbital cellulitis that is nonresponsive to antibiotics and reviews the clinicopathologic nature of this disease.
Olsen M, Lyngstadaas A, Bair J, Hodges R, Utheim T, Serhan C, Dartt DA. Signaling Pathways Used by the Specialized Pro-Resolving Mediator Maresin 2 Regulate Goblet Cell Function: Comparison with Maresin 1. Int J Mol Sci. 2022;23(11).
Specialized pro-resolving mediators (SPMs), including Maresins (MaR)-1 and 2, contribute to tear film homeostasis and resolve conjunctival inflammation. We investigated MaR2's signaling pathways in goblet cells (GC) from rat conjunctiva. Agonist-induced [Ca2+]i and high-molecular weight glycoconjugate secretion were measured. MaR2 increased [Ca2+]i and stimulated secretion. MaR2 and MaR1 stimulate conjunctival goblet cell function, especially secretion, by activating different but overlapping GPCR and signaling pathways, and furthermore counter-regulate histamine stimulated increase in [Ca2+]i. Thus, MaR2 and MaR1 play a role in maintaining the ocular surface and tear film homeostasis in health and disease. As MaR2 and MaR1 modulate conjunctival goblet cell function, they each may have potential as novel, but differing, options for the treatment of ocular surface inflammatory diseases including allergic conjunctivitis and dry eye disease. We conclude that in conjunctival GC MaR2 and MaR1, both increase the [Ca2+]i and stimulate secretion to maintain homeostasis by using one set of different, but overlapping, signaling pathways to increase [Ca2+]i and another set to stimulate secretion. MaR2 also resolves ocular allergy.
Sekimitsu S, Wang J, Elze T, Segrè A, Wiggs J, Zebardast N. Interaction of background genetic risk, psychotropic medications, and primary angle closure glaucoma in the UK Biobank. PLoS One. 2022;17(6):e0270530.
BACKGROUND/AIMS: Psychotropic medications have been reported as a risk factor for angle closure disease. However, the interaction between background genetic risk for primary angle closure glaucoma (PACG) and susceptibility to angle closure disease among psychotropic medication users has not been investigated. Here we demonstrate the utility of a genome-wide polygenic risk score (PRS) in identifying and risk-stratifying subjects with PACG and investigate the association between PACG genetic burden and exposure to psychotropic medications on prevalent angle closure. METHODS: This analysis used the UK Biobank dataset, a prospective cohort study of 502,506 UK residents. We constructed a PACG PRS for participants using genome-wide association study summary statistics from a multiethnic meta-analysis using the Lassosum method. RESULTS: Among the 441,054 participants, 959 (0.22%) were identified as PACG cases. Individuals with PACG had higher PRS compared to those without PACG (0.24±1.03 SD vs. 0.00±1.00 SD, p<0.001) and PACG prevalence increased with each decile of higher PRS. Among individuals using psychotropic medication, those with PACG had higher average PRS (0.31±1.00 SD vs. 0.00±1.00 SD, p<0.001) and were more likely to have a PRS in upper deciles of polygenic risk (p = 0.04). At each decile of PRS, psychotropic medication use was associated with increased risk of PACG. These effects were more pronounced and significant in higher deciles. CONCLUSION: We demonstrate the utility of a PRS for identifying individuals at higher risk of PACG. Additionally, we demonstrate an important relationship where the association between psychotropic medications use and PACG diagnosis varies across the polygenic risk spectrum.
Wang F, Liu LQ, Liang RB, Zhang LJ, Shu HY, Liao XL, Pan YC, Wu J, Su T, Shao Y. Decreased Macular Retinal Thickness in Patients With Pterygium. Front Neurol. 2022;13:881190.
Purpose: To explore alterations in macular retinal thickness (RT) and analyze correlation between macular RT and pterygium area, length in pterygium patients. Methods: Totally 13 patients with pterygium (left eye) and 13 healthy controls (left eye) were recruited. OCTA was applied to scan each eye to generate three-dimensional images. Based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method, each image was divided into nine subregions for the ETDRS: central (C); inner superior (IS); outer superior (OS); inner nasal (IN); outer nasal (ON); inner inferior (II); outer inferior (OI); inner temporal (IT); and outer temporal (OT). The macular RT in each subregion was measured. Furthermore, the correlation between RT and the area, length of pterygium was analyzed. Results: The visual acuity of pterygium patient was different from that of the control (P < 0.05). Besides, decreased intraretinal thickness of the IN and ON, increased intraretinal thickness of OT, decreased extraretinal thickness of OT, IN, ON, OS, and decreased retinal full layer thickness of medial superior, OS, IN, ON, and II subregions in pterygium group were observed. There was a negative correlation between RT of the IN and ON subregions and the length of pterygium (r = -0.5803 and r = -0.6013, P = 0.0376 and P = 0.0297). The RT of IN subregion was negatively correlated with pterygium area (r = -0.5844, P = 0.0359). According to the receiver operating characteristic analysis, in the ON subregion, the areas under the curve of the inner retinal thickness, outer retinal thickness and the whole retinal thickness were 1.0 (95% CI: 1.0), 0.882 (95% CI: 0.715 and 0.963), and 1.0 (95% CI: 1.0). The smallest area under the curve of retinal thickness in OT subregion was 0.018 (95% CI: 0-0.059). Conclusion: RT of pterygium patients was significantly decreased, and the main alterations occurred in the temporal side suggesting there might exist retinal structural alterations in pterygium.
Oke I, Lorenz B, Basiakos S, Gokyigit B, Ugo Dodd MM, Laurent E, Hunter D, Goberville M, Elkamshoushy A, Tsai CB, Orge F, Velez F, Jeddawi L, Gravier N, Li N, Shah A, Dagi L, NTSLR3NP Study Group. Nasal Transposition of the Split Lateral Rectus Muscle for Strabismus Associated With Bilateral 3rd-Nerve Palsy. Am J Ophthalmol. 2022;242:165–172.
PURPOSE: To determine the success rate and complications associated with nasal transposition of the split lateral rectus muscle (NTSLR) for treating bilateral 3rd-nerve palsy. DESIGN: Retrospective, interventional case series. METHODS: An international, multicenter registry was used for the study. The study population was all patients with bilateral 3rd-nerve palsy treated with NTSLR. Sensorimotor evaluations were conducted before and 6 months after unilateral or bilateral NTSLR. Outcome measures were postoperative horizontal alignment ≤15 prism diopters (PD), intraoperative technical difficulties, and vision-threatening complications. The association of patient demographics and surgical technique with each outcome was analyzed using multivariable logistic regression. RESULTS: A total of 34 patients were included, with a median age of 46 years (interquartile range [IQR] = 25-54 years) at surgery. The most common etiologies were ischemic (29%), neoplastic (15%), and congenital (12%). NTSLR performed unilaterally with alternative surgery on the opposite eye (65%) resulted in a median postoperative exotropia of 18 PD (IQR = 7-35 PD), and when performed bilaterally (35%) resulted in postoperative exotropia of 14 PD (IQR = 5-35 PD). Success was achieved in 50% of cases, intraoperative technical difficulties were reported in 18%, and vision-threatening complications occurred in 21%. Attachment of the lateral rectus muscle ≥10 mm posterior to the medial rectus insertion was associated with increased vision-threatening complications (odds ratio = 9.0; 95% CI = 1.3-99). CONCLUSIONS: NTSLR can address the large-angle exotropia associated with bilateral 3rd-nerve palsy. Surgeons should be aware that posterior placement of the lateral rectus muscle may increase the risk of vision-threatening complications, particularly serous choroidal effusion.
White E, Walsh L. The Impact of Occlusion Therapy on Amblyopia Success Outcomes. J Binocul Vis Ocul Motil. 2022;72(3):183–190.
PURPOSE: The recommended amount of occlusion therapy and amblyopia treatment success rates remains controversial. This study explores rates of occlusion therapy success and attempts to address limitations of previous literature. METHODS: A retrospective chart review was performed on patients with occlusion therapy outcomes from 2012 to 2019. Equal visual acuity (VA) or stable VA for three consecutive clinical visits, despite reported good compliance defined outcome VA. RESULTS: Results showed 90.3% of subjects obtained outcome distance VA of 0.3logMAR, 76% ≥0.3logMAR, 35% ≥0.2logMAR, and 6% ≥0.1logMAR in the amblyopic eye following treatment. Sixty-nine percent of the study population obtained equal vision following occlusion therapy. Only initial VA (amblyopic eye) and initial interocular visual optotype difference at distance predicted post-treatment success. CONCLUSION: These results support the conclusion that occlusion therapy, both PTO and FTO, can be effective in treating amblyopia when good compliance is maintained based on parental reports of compliance. Additionally, as VA gain was higher than in previous literature, it is important to continue treatment until VA is equal or three consecutive cycles of stable VA are obtained to ensure maximum VA improvement.