2022

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Hanyuda A, Rosner BA, Wiggs JL, Negishi K, Pasquale LR, Kang JH. Long-Term Alcohol Consumption and Risk of Exfoliation Glaucoma/Glaucoma Suspect among US Health Professionals. Ophthalmology 2022;
Harris CK, Christensen BB, Kwan M, Foreman RK, Stagner AM. Pseudomonas species may appear strikingly filamentous in tissue sections: an important consideration for surgical pathologists and a reminder of the utility of modified silver impregnation methods. Histopathology 2022;Abstract
INTRODUCTION: Although tissue culture is the gold standard for diagnosing infection, histologic examination of surgically resected tissue can be a critical component in the diagnosis of tissue infection. The goal of this brief report is to alert surgical pathologists that Pseudomonas species can appear strikingly filamentous histologically and may somewhat mimic the appearance of filamentous bacteria, such Actinomyces or Nocardia, or thin fungal hyphae. A secondary aim is to raise awareness that Pseudomonas can sometimes only be identified histologically through the use of a modified silver impregnation method (Steiner stain). METHODS: Five cases of filamentous Pseudomonas were encountered in three different surgical pathology subspecialities (ophthalmic pathology, cardiovascular pathology, and dermatopathology) over a 1-year period. All cases were of formalin-fixed, paraffin-embedded tissue, stained using hematoxylin & eosin (H&E) and multiple histochemical stains. Four cases grew Pseudomonas aeruginosa in culture and in the fifth case, a non-aeruginosa species was detected using polymerase chain reaction-based methods. RESULTS: Five cases of markedly filamentous-appearing Pseudomonas were identified in five different tissue sites: vascular graft, enucleation (whole eye) specimen, scleral biopsy, soft tissue excision, and skin punch biopsy. In one of the five cases were the organisms seen on H&E and in only two of the five were the organisms seen on Brown-Hopps stain. In all five cases, the organisms were identified on Steiner stain. DISCUSSION: Pseudomonas can appear markedly filamentous. If Pseudomonas or other bacterial infection is suspected, the surgical pathologist would be advised to employ the Steiner stain to most consistently detect the organisms.
Haseeb A, Elhusseiny AM, ElSheikh RH, Tahboub MA, Kwan JT, Saeed HN. Ocular involvement in Mycoplasma induced rash and mucositis: A systematic review of the literature. Ocul Surf 2022;Abstract
Mycoplasma pneumoniae induced rash and mucositis (MIRM) is a relatively newly identified clinical entity which is characterized by mucocutaneous manifestations in the setting of Mycoplasma infection. Though a clinically distinct disease, MIRM exists on a diagnostic continuum with entities including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and the recently described reactive infectious mucocutaneous eruption (RIME). In this systematic review, we discuss published findings on the epidemiology, clinical manifestations, diagnosis, and management of MIRM, with an emphasis on ocular disease. Lastly, we discuss some of the most recent developments and challenges in characterizing MIRM with respect to the related diagnosis of RIME.
He B, Tanya SM, Wang C, Kezouh A, Torun N, Ing E. The Incidence of Sympathetic Ophthalmia After Trauma: A Meta-analysis. Am J Ophthalmol 2022;234:117-125.Abstract
PURPOSE: Sympathetic ophthalmia (SO) is a rare, bilateral panuveitis that occurs following open globe injury (OGI), with a variable incidence reported in the literature. Our objective was to determine the incidence proportion and incidence rate of SO following OGI to help guide shared physician-patient decision making. DESIGN: Systematic review and meta-analysis. METHODS: A systematic literature search was performed using the MEDLINE, EMBASE, and Cochrane databases from inception to November 2020 for population-based studies on OGI and SO in adults and children. Two reviewers independently screened search results. Random-effects meta-analyses were performed to calculate the incidence proportion and incidence rate. The Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool was used to assess the risk of bias. The study was registered on PROSPERO CRD42020198920. RESULTS: A total of 24 studies were utilized in the meta-analyses. After OGI, the estimated overall incidence proportion of SO was 0.19% (95% CI 0.14%-0.24%) and the incidence rate of SO was 33 per 100,000 person-years, (95% CI 19.61-56.64) with I2 of 13% and 72%, respectively. CONCLUSIONS: SO after OGI is rare. The estimated incidence proportion and incidence rate are useful when counselling patients regarding management options after OGI. Further studies are needed to examine the influence of age, the extent and location of trauma, timing of repair, and prophylactic eye removal on the incidence of SO.
Heckel E, Cagnone G, Agnihotri T, Cakir B, Das A, Kim JS, Kim N, Lavoie G, Situ A, Pundir S, Sun Y, Wünnemann F, Pierce KA, Dennis C, Mitchell GA, Chemtob S, Rezende FA, Andelfinger G, Clish CB, Roux PP, Sapieha P, Smith LEH, Joyal J-S. Triglyceride-derived fatty acids reduce autophagy in a model of retinal angiomatous proliferation. JCI Insight 2022;7(6)Abstract
Dyslipidemia and autophagy have been implicated in the pathogenesis of blinding neovascular age-related macular degeneration (NV-AMD). VLDL receptor (VLDLR), expressed in photoreceptors with a high metabolic rate, facilitates the uptake of triglyceride-derived fatty acids. Since fatty acid uptake is reduced in Vldlr-/- tissues, more remain in circulation, and the retina is fuel deficient, driving the formation in mice of neovascular lesions reminiscent of retinal angiomatous proliferation (RAP), a subtype of NV-AMD. Nutrient scarcity and energy failure are classically mitigated by increasing autophagy. We found that excess circulating lipids restrained retinal autophagy, which contributed to pathological angiogenesis in the Vldlr-/- RAP model. Triglyceride-derived fatty acid sensed by free fatty acid receptor 1 (FFAR1) restricted autophagy and oxidative metabolism in photoreceptors. FFAR1 suppressed transcription factor EB (TFEB), a master regulator of autophagy and lipid metabolism. Reduced TFEB, in turn, decreased sirtuin-3 expression and mitochondrial respiration. Metabolomic signatures of mouse RAP-like retinas were consistent with a role in promoting angiogenesis. This signature was also found in human NV-AMD vitreous. Restoring photoreceptor autophagy in Vldlr-/- retinas, either pharmacologically or by deleting Ffar1, enhanced metabolic efficiency and suppressed pathological angiogenesis. Dysregulated autophagy by circulating lipids might therefore contribute to the energy failure of photoreceptors driving neovascular eye diseases, and FFAR1 may be a target for intervention.
Heidary G, Aakalu VK, Binenbaum G, Chang MY, Morrison DG, VanderVeen DK, Lambert SR, Trivedi RH, Galvin JA, Pineles SL. Adjustable Sutures in the Treatment of Strabismus: A Report by the American Academy of Ophthalmology. Ophthalmology 2022;129(1):100-109.Abstract
PURPOSE: To review the scientific literature that evaluates the effectiveness of adjustable sutures in the management of strabismus for adult and pediatric patients. METHODS: Literature searches were performed in the PubMed database through April 2021 with no date limitations and were restricted to publications in English. The searches identified 551 relevant citations, of which 55 were reviewed in full text. Of these, 17 articles met the inclusion criteria and were assigned a level of evidence rating by the panel methodologist. The search included all randomized controlled studies regardless of study size and cohort studies of 100 or more patients comparing the adjustable versus nonadjustable suture technique, with a focus on motor alignment outcomes or reoperation rates. RESULTS: The literature search yielded no level I studies. Of the 17 articles that met the inclusion criteria, 11 were rated level II and 6 were rated level III. Among the 12 studies that focused on motor alignment outcomes, 4 small randomized clinical trials (RCTs) did not find a statistically significant difference between groups, although they were powered to detect only very large differences. Seven of 8 nonrandomized studies found a statistically significant difference in motor alignment success in favor of the adjustable suture technique, both overall and in certain subgroups of patients. Successful motor alignment was seen in both exotropia (in 3 studies that were not limited to children) and esotropia (in 1 study of adults and 2 of children). The majority of included studies that reported on reoperation rates found the rates to be lower in patients who underwent strabismus surgery with adjustable sutures, but this finding was not uniformly demonstrated. CONCLUSIONS: Although there are no level I studies evaluating the effectiveness of adjustable sutures for strabismus surgery, the majority of nonrandomized studies that met the inclusion criteria for this assessment reported an advantage of the adjustable suture technique over the nonadjustable technique with respect to motor alignment outcomes. This finding was not uniformly demonstrated among all studies reviewed and warrants further investigation in the development and analysis of adjustable suture techniques.
Hellström A, Jacobson L, Al-Hawasi A, Hellström-Westas L, Rakow A, Johnson M, Sävman K, Holmstrom G, Larsson E, Gränse L, Saric M, Sunnqvist B, Smith L, Hård AL, Morsing E, Lundgren P. Retrospective evaluation of ophthalmological and neurological outcomes for infants born before 24 weeks gestational age in a Swedish cohort. BMJ Open 2022;
Henao-Restrepo J, López-Murillo C, Valderrama-Carmona P, Orozco-Santa N, Gomez J, Gutiérrez-Vargas J, Moraga R, Toledo J, Littau JL, Härtel S, Arboleda-Velásquez JF, Sepulveda-Falla D, Lopera F, Cardona-Gómez GP, Villegas A, Posada-Duque R. Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection. Brain Pathol 2022;:e13119.Abstract
In response to brain insults, astrocytes become reactive, promoting protection and tissue repair. However, astroglial reactivity is typical of brain pathologies, including Alzheimer's disease (AD). Considering the heterogeneity of the reactive response, the role of astrocytes in the course of different forms of AD has been underestimated. Colombia has the largest human group known to have familial AD (FAD). This group carries the autosomal dominant and fully penetrant mutation E280A in PSEN1, which causes early-onset AD. Recently, our group identified an E280A carrier who did not develop FAD. The individual was homozygous for the Christchurch mutation R136S in APOE3 (APOEch). Remarkably, APOE is the main genetic risk factor for developing sporadic AD (SAD) and most of cerebral ApoE is produced by astroglia. Here, we characterized astrocyte properties related to reactivity, glutamate homeostasis, and structural integrity of the gliovascular unit (GVU), as factors that could underlie the pathogenesis or protection of AD. Specifically, through histological and 3D microscopy analyses of postmortem samples, we briefly describe the histopathology and cytoarchitecture of the frontal cortex of SAD, FAD, and APOEch, and demonstrate that, while astrodegeneration and vascular deterioration are prominent in SAD, FAD is characterized by hyperreactive-like glia, and APOEch displays the mildest astrocytic and vascular alterations despite having the highest burden of Aβ. Notably, astroglial, gliovascular, and vascular disturbances, as well as brain cell death, correlate with the specific astrocytic phenotypes identified in each condition. This study provides new insights into the potential relevance of the gliovasculature in the development and protection of AD. To our knowledge, this is the first study assessing the components of the GVU in human samples of SAD, FAD, and APOEch.
Ho TC, Maamari RN, Kossler AL, Sears CM, Freitag SK, Reshef ER, Shinder R, Rootman DB, Diniz SB, Kahana A, Schlachter D, Do TH, Kally P, Turner S, Mokhtarzadeh A, Harrison AR, Hwang CJ, Kim HJ, Avila SA, Thomas DA, Magazin M, Wester ST, Lee WW, Clauss KD, Holds JB, Sniegowski M, Compton CJ, Briggs C, Malik AI, Lucarelli MJ, Burkat CN, Patel LG, Couch SM. Outcomes of Patients With Thyroid Eye Disease Partially Treated With Teprotumumab. Ophthalmic Plast Reconstr Surg 2022;Abstract
PURPOSE: In response to the coronavirus (COVID-19) pandemic, teprotumumab production was temporarily halted with resources diverted toward vaccine production. Many patients who initiated treatment with teprotumumab for thyroid eye disease were forced to deviate from the standard protocol. This study investigates the response of teprotumumab when patients receive fewer than the standard 8-dose regimen. METHODS: This observational cross-sectional cohort study included patients from 15 institutions with active or minimal to no clinical activity thyroid eye disease treated with the standard teprotumumab infusion protocol. Patients were included if they had completed at least 1 teprotumumab infusion and had not yet completed all 8 planned infusions. Data were collected before teprotumumab initiation, within 3 weeks of last dose before interruption, and at the visit before teprotumumab reinitiation. The primary outcome measure was reduction in proptosis more than 2 mm. Secondary outcome measures included change in clinical activity score (CAS), extraocular motility restriction, margin reflex distance-1 (MRD1), and reported adverse events. RESULTS: The study included 74 patients. Mean age was 57.8 years, and 77% were female. There were 62 active and 12 minimal to no clinical activity patients. Patients completed an average of 4.2 teprotumumab infusions before interruption. A significant mean reduction in proptosis (-2.9 mm in active and -2.8 mm in minimal to no clinical activity patients, P < 0.01) was noted and maintained during interruption. For active patients, a 3.4-point reduction in CAS (P < 0.01) and reduction in ocular motility restriction (P < 0.01) were maintained during interruption. CONCLUSIONS: Patients partially treated with teprotumumab achieve significant reduction in proptosis, CAS, and extraocular muscle restriction and maintain these improvements through the period of interruption.
Hoogsteen KMP, Szpiro S, Kreiman G, Peli E. Beyond the Cane: Describing Urban Scenes to Blind People for Mobility Tasks. ACM Trans Access Comput 2022;15(3)Abstract
Blind people face difficulties with independent mobility, impacting employment prospects, social inclusion, and quality of life. Given the advancements in computer vision, with more efficient and effective automated information extraction from visual scenes, it is important to determine what information is worth conveying to blind travelers, especially since people have a limited capacity to receive and process sensory information. We aimed to investigate which objects in a street scene are useful to describe and how those objects should be described. Thirteen cane-using participants, five of whom were early blind, took part in two urban walking experiments. In the first experiment, participants were asked to voice their information needs in the form of questions to the experimenter. In the second experiment, participants were asked to score scene descriptions and navigation instructions, provided by the experimenter, in terms of their usefulness. The descriptions included a variety of objects with various annotations per object. Additionally, we asked participants to rank order the objects and the different descriptions per object in terms of priority and explain why the provided information is or is not useful to them. The results reveal differences between early and late blind participants. Late blind participants requested information more frequently and prioritized information about objects' locations. Our results illustrate how different factors, such as the level of detail, relative position, and what type of information is provided when describing an object, affected the usefulness of scene descriptions. Participants explained how they (indirectly) used information, but they were frequently unable to explain their ratings. The results distinguish between various types of travel information, underscore the importance of featuring these types at multiple levels of abstraction, and highlight gaps in current understanding of travel information needs. Elucidating the information needs of blind travelers is critical for the development of more useful assistive technologies.
Houston KE, Paschalis EI. Feasibility of Magnetic Levator Prosthesis Frame Customization Using Craniofacial Scans and 3-D Printing. Transl Vis Sci Technol 2022;11(10):34.Abstract
Purpose: To determine the feasibility of a custom frame generation approach for nonsurgical management of severe blepharoptosis with the magnetic levator prosthesis (MLP). Methods: Participants (n = 8) with severe blepharoptosis (obscuring the visual axis) in one or both eyes who had previously been using a non-custom MLP had a craniofacial scan with a smartphone app to generate a custom MLP frame. A magnetic adhesive was attached to the affected eyelid. The custom MLP frame held a cylindrical magnet near the eyebrow above the affected eyelid, suspending it in the magnetic field while still allowing blinking. The spectacle magnet could be rotated manually, providing adjustable force via angular translation of the magnetic field. Fitting success and comfort were recorded, and interpalpebral fissure (IPF) was measured from video frames after 20 minutes in-office and one-week at-home use. Preference was documented, custom versus non-custom. Results: Overall, 88% of patients (7/8) were successfully fitted with a median 9/10 comfort (interquartile 7-10) and median ptosis improvement of 2.3 mm (1.3-5.0); P = 0.01). Exact binomial testing suggested, with 80% power, that the true population success rate was significantly greater than 45% (P = 0.05). Five participants took the custom MLP home for one week, with only one case of mild conjunctival redness which resolved without treatment. Highest to lowest force modulation resulted in a marginally significant median IPF adjustment of 1.5 mm (0.8 to 2.7; P = 0.06). All preferred the custom frame. Conclusions: The three-dimensional custom MLP frame generation approach using a smartphone app-based craniofacial scan is a feasible approach for clinical deployment of the MLP. Translational Relevance: First demonstration of customized frame generation for the MLP.
Hoyek S, Aronow ME, Patel NA. Posterior Scleral Cyst in a Pediatric Patient. Ophthalmology 2022;129(5):529.
Hoyek S, Wang M, Berrocal AM, Wong A, Place EM, Mason-Suares H, Lin AE, Mukai S, Patel NA. Combined X-linked familial exudative vitreoretinopathy and retinopathy of prematurity phenotype in an infant with mosaic turner syndrome with ring X chromosome. Ophthalmic Genet 2022;:1-6.Abstract
BACKGROUND: Retinopathy of prematurity (ROP) and familial exudative vitreoretinopathy (FEVR) are two distinct pathologies of retinal angiogenesis with overlapping clinical features. METHODS: Examination, multimodal imaging, and genetic testing were used to guide diagnosis and treatment. RESULTS: We report a combined phenotype of X-linked FEVR and ROP in a 4-month-old girl with mosaic Turner syndrome with ring X chromosome born at 26 weeks gestational age. She was initially diagnosed with atypical ROP with a vitreous band causing a localized traction retinal detachment, inferotemporal to the macula in the right eye, vessels to posterior zone 2 with no clear ridge temporally in the left eye, and fluorescein leakage in both eyes. Due to the suspicion of concurrent FEVR, genetic testing using a vitreoretinopathy panel was performed which revealed a mosaic Turner syndrome associated with 45,X/46,X,r(X), subsequently confirmed by chromosome analysis. The deleted region in the ring X chromosome included the NDP and RS1 genes. The patient was treated with laser photocoagulation of the peripheral avascular retina and sub-Tenon's triamcinolone injection in both eyes, intravitreal injection of bevacizumab in the left eye, and pars plicata vitrectomy in the right eye. CONCLUSIONS: In premature neonates with atypical ROP, a clinical suspicion of concurrent FEVR or similar vasculopathy is important and genetic testing may elucidate a genetic etiology, which could influence management and prognosis. Turner syndrome can be connected with co-occurring Mendelian gene disorders, particularly in individuals with mosaicism. The concurrence of FEVR and ROP appears to result in atypical and possibly more severe phenotypes.
Hoyek S, Peacker BL, Acaba-Berrocal LA, Al-Khersan H, Zhao Y, Hartnett ME, Berrocal AM, Patel NA. The Male to Female Ratio in Treatment-Warranted Retinopathy of Prematurity: A Systematic Review and Meta-analysis. JAMA Ophthalmol 2022;140(11):1110-1120.Abstract
IMPORTANCE: Literature and anecdotal evidence suggest a relationship between male sex and retinopathy of prematurity (ROP). It is not known whether a difference, if present, is sex-related pathophysiologic predisposition or sex difference in meeting ROP screening criteria. OBJECTIVE: To evaluate the association of sex with the development of treatment-warranted ROP. DATA SOURCES: PubMed, Embase, and Web of Science databases were searched from 2000 to 2022. The search strategy used keywords including retinopathy of prematurity or ROP or retrolental fibroplasia and treatment or anti-VEGF or bevacizumab or ranibizumab or aflibercept or conbercept or laser or cryotherapy and gender or sex or male or female and medical subject headings terms. STUDY SELECTION: All studies reporting on treatment with anti-vascular endothelial growth factor, laser photocoagulation, and/or cryotherapy for ROP were identified. Studies reporting sex distribution in the treatment group were included in the meta-analysis. Exclusion criteria included case reports, case series of fewer than 10 treated patients, systematic reviews, conference abstracts, letters to the editor, animal studies, and non-English records. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened and extracted the data following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The proportions of treated male and female infants were combined using random-effects meta-analysis. MAIN OUTCOMES AND MEASURES: Numbers and percentages of male and female infants treated for ROP. RESULTS: Of 11 368 identified studies, 316 met inclusion criteria, yielding a total of 31 026 treated patients. A higher percentage of male infants were treated for ROP (55% [95% CI, 0.54%-0.55%]), with low heterogeneity between studies (I2 = 34%; P < .001). Thirty-eight studies reported sex distribution in the screened population (170 053 patients; 92 612 [53%] male vs 77 441 [47%] female). There was no significant difference in the odds of receiving treatment between screened male and female infants (pooled odds ratio, 1.04 [95% CI, 0.91-1.18]; P = .67). CONCLUSIONS AND RELEVANCE: More male infants are treated for ROP than female infants. This could be due to a known relative pathophysiological fragility of preterm male infants in addition to a difference in ROP screening rates, with more male infants meeting the criteria than female infants. These findings have implications for future studies and may prompt more careful clinical monitoring of male neonates.
Hu B, Huang Y, Jakobs TC, Kang Q, Lv Z, Liu W, Wang R. Viability of mitochondria-labeled retinal ganglion cells in organotypic retinal explant cultures by two methods. Exp Eye Res 2022;:109311.Abstract
Retinal explant cultures provide a valuable system to study retinal function in vitro. This study establishes a new retinal explant culture method to prolong the survival of retinal ganglion cells (RGCs). Explants were prepared in two different ways: with or without optic nerve. Retinas from newborn mice that had received an injection of MitoTracker Red into the contralateral superior colliculus to label axonal mitochondria were cultured as organotypic culture for 7 days in vitro. At several time points during the culture, viability of RGCs was assessed by multi-electrode array recording, and morphology by immunohistochemical methods. During the culture, the thickness of the retinal tissue in both groups gradually decreased, however, the structure of the layers of the retina could be identified. Massive apoptosis in the retinal ganglion cell layer (GCL) appeared on the first day of culture, thereafter the number of apoptotic cells decreased. Glial activation was observed throughout the culture, and there was no difference in morphology between the two groups. RGCs loss was exacerbated on 3rdday of culture, and RGCs loss in retinal explants with preserved optic nerve was significantly lower than in retinas that did not preserve the optic nerve. More and longer-lasting mitochondrial signals were observed in the injured area of the optic nerve-preserving explants. Retinal explants provide an invaluable tool for studying retinal function and developing treatments for ocular diseases. The optic nerve-preserving culture helps preserve the integrity of RGCs. The higher number of mitochondria in the nerve-preserving cultures may help maintain viability of RGCs.
Hu XQ, Shi YD, Chen J, You Z, Pan YC, Ling Q, Wei H, Zou J, Ying P, Liao XL, Su T, Wang YX, Shao Y. Children with strabismus and amblyopia presented abnormal spontaneous brain activities measured through fractional amplitude of low-frequency fluctuation (fALFF). Front Neurol 2022;
Huang T, Liang R-B, Zhang L-J, Shu H-Y, Ge Q-M, Liao X-L, Wu J-L, Su T, Pan Y-C, Zhou Q, Shao Y. Retinal microvasculature alteration in patients with systemic sclerosis and chloroquine treatment. Quant Imaging Med Surg 2022;12(10):4885-4899.Abstract
Background: Retinal vascular abnormality is an important part of ocular systemic sclerosis (SSc), and long-term use of chloroquine can lead to retinal toxicity. This study was conducted to evaluate retinal microvascular changes using optical coherence tomography angiography (OCTA) in patients with SSc and SSc patients on long-term chloroquine treatment. Methods: Fifteen SSc patients without chloroquine (30 eyes), 15 SSc patients taking long-term chloroquine (30 eyes) and 15 healthy controls (30 eyes) were recruited to this cross-sectional study. OCTA was used to examine the superficial and deep retinal capillary plexus in the macular retina of each eye. The densities of microvessels (MIR), macrovessels (MAR) and total microvessels (TMI) in the superficial and deep retina of the three groups were calculated and compared. We used the hemisphere segmentation method [superior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)] and Early Treatment Diabetic Retinopathy Study (ETDRS) method [right (R), superior (S), left (L), and inferior (I)] to analyze changes in retinal microvascular density. Results: The superficial and deep retinal MIR density in SSc patients decreased (P<0.05) compared with the healthy control group. This significant difference was found in both superficial and deep layers in S, L, SR, SL and IL regions (P<0.05), and additionally in the R and I regions in the superficial layer (P<0.05). Similarly, compared with SSc patients who did not take chloroquine, the superficial and deep retinal MIR density of SSc patients on long-term chloroquine also decreased (P<0.05). This significant difference was found in both superficial and deep layers in R, I and IL regions (P<0.05), and additionally in the IR region in the superficial layer (P<0.05). Conclusions: The OCTA results suggest that retinal MIR density is decreased in SSc patients, and that long-term use of chloroquine will aggravate this damage, resulting in a further decrease in retinal MIR density.
Huang JJ, Geduldig JE, Jacobs EB, Tai TYT, Ahmad S, Chadha N, Buxton DF, Vinod K, Wirostko BM, Kang JH, Wiggs JL, Ritch R, Pasquale LR. Head and Neck Region Dermatological Ultraviolet-Related Cancers are Associated with Exfoliation Syndrome in a Clinic-Based Population. Ophthalmol Glaucoma 2022;5(6):663-671.Abstract
OBJECTIVE: We assessed the relationship between ultraviolet (UV)-associated dermatological carcinomas (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) and exfoliation syndrome (XFS) or exfoliation glaucoma (XFG). DESIGN: Case-control study. PARTICIPANTS: Between 2019 and 2021, 321 participants and control subjects (XFS or XFG = 98; primary open-angle glaucoma [POAG] = 117; controls = 106; ages 50-90 years) were recruited. METHODS: A cross-sectional survey assessing medical history, maximum known intraocular pressure, cup-to-disc ratio, Humphrey visual field 24-2, the propensity to tan or burn in early life, history of BCC or SCC, and XFS or XFG diagnosis. The multivariable models adjusted for age, sex, medical history, eye color, hair color, and likeliness of tanning versus burning at a young age. MAIN OUTCOME MEASURES: History of diagnosed XFS or XFG. RESULTS: Any history of BCC or SCC in the head and neck region was associated with a 2-fold higher risk of having XFS or XFG versus having POAG or being a control subject (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.04-3.89) in a multivariable-adjusted analysis. We observed a dose-response association in which the chance of having XFS or XFG increased by 67% per head and neck BCC or SCC occurrence (OR, 1.67; 95% CI, 1.09-2.56). When we excluded POAG participants, head and neck BCC or SCC was associated with a 2.8-fold higher risk of XFS or XFG (OR, 2.80; 95% CI, 1.12-7.02), and each additional occurrence had a 2-fold higher risk of XFS or XFG (OR, 1.97; 95% CI, 1.09-3.58). The association between head and neck region BCC or SCC and POAG compared with the control subjects was null (OR, 1.42; 95% CI, 0.58-3.48). With BCC or SCC located anywhere on the body, there was a nonsignificantly higher risk of having XFS or XFG compared with having POAG or being a control subject (OR, 1.65; 95% CI, 0.88-3.09). CONCLUSIONS: Head and neck region BCCs or SCCs are associated with a higher risk of having XFS or XFG. These findings support prior evidence that head and neck UV exposure may be a risk factor for XFS.
Huang X, Saki F, Wang M, Elze T, Boland MV, Pasquale LR, Johnson CA, Yousefi S. An Objective and Easy-to-Use Glaucoma Functional Severity Staging System Based on Artificial Intelligence. J Glaucoma 2022;Abstract
OBJECTIVE: To develop an objective and easy-to-use glaucoma staging system based on visual fields (VFs). SUBJECTS AND PARTICIPANTS: A total of 13,231 VFs from 8077 subjects were used to develop models and 8024 VFs from 4445 subjects were used to validate models. METHODS: We developed an unsupervised machine learning model to identify clusters with similar VF values. We annotated the clusters based on their respective mean deviation (MD). We computed optimal MD thresholds that discriminate clusters with highest accuracy based on Bayes minimum error principle. We evaluated the accuracy of the staging system and validated findings based on an independent validation dataset. RESULTS: The unsupervised k-means algorithm discovered four clusters with 6784, 4034, 1541, and 872 VFs and average MDs of 0.0▒dB (±1.4: Standard Deviation), -4.8▒dB (±1.9), -12.2▒dB (±2.9), and -23.0▒dB (±3.8), respectively. The supervised Bayes minimum error classifier identified optimal MD thresholds of -2.2▒dB, -8.0▒dB, and -17.3▒dB for discriminating normal eyes and eyes at the early, moderate, and advanced stages of glaucoma. The accuracy of the glaucoma staging system was 94%, based on identified MD thresholds with respect to the initial k-means clusters. CONCLUSIONS: We discovered that four severity levels based on MD thresholds of -2.2▒dB, -8.0▒dB, and -17.3▒dB, provides the optimal number of severity stages based on unsupervised and supervised machine learning. This glaucoma staging system is unbiased, objective, easy-to-use, and consistent, which makes it highly suitable for use in glaucoma research and for day-to-day clinical practice.
Huang YY, Hrycaj SM, Chan MP, Stagner AM, Patel RM, Bresler SC. PRAME Expression in Junctional Melanocytic Proliferations of the Conjunctiva: A Potential Biomarker for Primary Acquired Melanosis/Conjunctival Melanocytic Intraepithelial Lesions. Am J Dermatopathol 2022;44(10):734-740.Abstract
ABSTRACT: Conjunctival melanocytic proliferations are diagnostically challenging, often complicated by small specimen size, and are separated into 3 broad categories. The first group includes benign nevi and primary acquired melanosis (PAM) without atypia. The second group includes junctional melanocytic proliferations with a risk of progression to invasive melanoma (PAM with atypia). The last category is conjunctival melanoma, of which 65% of tumors arise in the setting of PAM with atypia. Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry has been widely adopted to differentiate cutaneous nevi and melanoma. However, there are limited studies on its utility in the evaluation of conjunctival melanocytic proliferations with little data regarding its potential utility in stratifying PAM. Twenty-eight clinically annotated cases (14 PAM without atypia and 14 PAM with atypia) were retrospectively evaluated with PRAME/MART-1 duplex immunohistochemistry and were assigned the commonly used PRAME immunoreactivity score: 0 for no staining, 1+ for 1%-25% of cells positive, 2+ for 26%-50%, 3+ for 51%-75%, and 4+ for >75%. PAM without atypia showed low (0-3+) PRAME expression in 14 of 14 cases (100%). PAM with atypia showed strong and diffuse (4+) PRAME expression in 12 of 14 cases (86.7%). Seven of eight (87.5%) PAM with severe atypia, 4 of 4 PAM (100%) with moderate atypia, and 1 of 2 PAM (50%) with mild atypia showed 4+ PRAME expression. In addition, all 5 cases that recurred or progressed (all classified as PAM with atypia) showed 4+ PRAME expression. Although additional larger studies are needed, PRAME seems to be a useful adjunct in evaluating junctional melanocytic proliferations of the conjunctiva.

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