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Manley CE, Bennett CR, Merabet LB. Assessing Higher-Order Visual Processing in Cerebral Visual Impairment Using Naturalistic Virtual-Reality-Based Visual Search Tasks. Children (Basel) 2022;9(8)Abstract
Cerebral visual impairment (CVI) is a brain-based disorder associated with the maldevelopment of central visual pathways. Individuals with CVI often report difficulties with daily visual search tasks such as finding a favorite toy or familiar person in cluttered and crowded scenes. We developed two novel virtual reality (VR)-based visual search tasks combined with eye tracking to objectively assess higher order processing abilities in CVI. The first (virtual toybox) simulates a static object search, while the second (virtual hallway) represents a dynamic human search task. Participants were instructed to search for a preselected target while task demand was manipulated with respect to the presence of surrounding distractors. We found that CVI participants (when compared to age-matched controls) showed an overall impairment with visual search on both tasks and with respect to all gaze metrics. Furthermore, CVI participants showed a trend of worsening performance with increasing task demand. Finally, search performance was also impaired in CVI participants with normal/near normal visual acuity, suggesting that reduced stimulus visibility alone does not account for these observations. This novel approach may have important clinical utility in helping to assess environmental factors related to functional visual processing difficulties observed in CVI.
Dave TV, Nair AG, Joseph J, Freitag SK. Immunopathology of COVID-19 and its implications in the development of rhino-orbital-cerebral mucormycosis: a major review. Orbit 2022;41(6):670-679.Abstract
PURPOSE: To present a literature review on various immunopathologic dysfunctions following COVID-19 infection and their potential implications in development of rhino-orbital-cerebral mucormycosis (ROCM). METHODS: A literature search was performed via Google Scholar and PubMed with subsequent review of the accompanying references. Analogies were drawn between the immune and physiologic deviations caused by COVID-19 and the tendency of the same to predispose to ROCM. RESULTS: Sixty-two articles were reviewed. SARS-CoV-2 virus infection leads to disruption of epithelial integrity in the respiratory passages, which may be a potential entry point for the ubiquitous Mucorales to become invasive. COVID-19 related GRP78 protein upregulation may aid in spore germination and hyphal invasion by Mucorales. COVID-19 causes interference in macrophage functioning by direct infection, a tendency for hyperglycemia, and creation of neutrophil extracellular traps. This affects innate immunity against Mucorales. Thrombocytopenia and reduction in the number of natural killer (NK) cells and infected dendritic cells is seen in COVID-19. This reduces the host immune response to pathogenic invasion by Mucorales. Cytokines released in COVID-19 cause mitochondrial dysfunction and accumulation of reactive oxygen species, which cause oxidative damage to the leucocytes. Hyperferritinemia also occurs in COVID-19 resulting in suppression of the hematopoietic proliferation of B- and T-lymphocytes. CONCLUSIONS: COVID-19 has a role in the occurrence of ROCM due to its effects at the entry point of the fungus in the respiratory mucosa, effects of the innate immune system, creation of an environment of iron overload, propagation of hyperglycemia, and effects on the adaptive immune system.
Aleman TS, Huckfeldt RM, Serrano LW, Pearson DJ, Vergilio GK, McCague S, Marshall KA, Ashtari M, Doan TM, Weigel-DiFranco CA, Biron BS, Wen X-H, Chung DC, Liu E, Ferenchak K, Morgan JIW, Pierce EA, Eliott D, Bennett J, Comander J, Maguire AM. Adeno-Associated Virus Serotype 2-hCHM Subretinal Delivery to the Macula in Choroideremia: Two-Year Interim Results of an Ongoing Phase I/II Gene Therapy Trial. Ophthalmology 2022;129(10):1177-1191.Abstract
PURPOSE: To assess the safety of the subretinal delivery of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human choroideremia (CHM)-encoding cDNA in CHM. DESIGN: Prospective, open-label, nonrandomized, dose-escalation, phase I/II clinical trial. PARTICIPANTS: Fifteen CHM patients (ages 20-57 years at dosing). METHODS: Patients received uniocular subfoveal injections of low-dose (up to 5 × 1010 vector genome [vg] per eye, n = 5) or high-dose (up to 1 × 1011 vg per eye, n = 10) of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human CHM-encoding cDNA (AAV2-hCHM). Patients were evaluated preoperatively and postoperatively for 2 years with ophthalmic examinations, multimodal retinal imaging, and psychophysical testing. MAIN OUTCOME MEASURES: Visual acuity, perimetry (10-2 protocol), spectral-domain OCT (SD-OCT), and short-wavelength fundus autofluorescence (SW-FAF). RESULTS: We detected no vector-related or systemic toxicities. Visual acuity returned to within 15 letters of baseline in all but 2 patients (1 developed acute foveal thinning, and 1 developed a macular hole); the rest showed no gross changes in foveal structure at 2 years. There were no significant differences between intervention and control eyes in mean light-adapted sensitivity by perimetry or in the lateral extent of retinal pigment epithelium relative preservation by SD-OCT and SW-FAF. Microperimetry showed nonsignificant (< 3 standard deviations of the intervisit variability) gains in sensitivity in some locations and participants in the intervention eye. There were no obvious dose-dependent relationships. CONCLUSIONS: Visual acuity was within 15 letters of baseline after the subfoveal AAV2-hCHM injections in 13 of 15 patients. Acute foveal thinning with unchanged perifoveal function in 1 patient and macular hole in 1 patient suggest foveal vulnerability to the subretinal injections. Longer observation intervals will help establish the significance of the minor differences in sensitivities and rate of disease progression observed between intervention and control eyes.
Kitazawa K, Inotmata T, Shih K, Hughes J-WB, 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.Abstract
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 KM, Stuart KV, Chua SYL, Foster PJ, Strouthidis NG, Luben RN, Warwick AN, Kang JH, Wiggs JL, Pasquale LR, Khawaja AP. The Association of Female Reproductive Factors with Glaucoma and Related Traits: A Systematic Review. Ophthalmol Glaucoma 2022;5(6):628-647.Abstract
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.
Elhusseiny AM, Saeed HN. Posterior Polymorphous Corneal Dystrophy in a Pediatric Population. Cornea 2022;41(6):734-739.Abstract
PURPOSE: The aim of this study was to evaluate the clinical and topographic features of posterior polymorphous corneal dystrophy (PPCD) in children aged 15 years or younger with a long-term follow-up. Retrospective case series. METHODS: A retrospective chart review of patients who were diagnosed with PPCD at Boston Children's Hospital from 1999 to 2020 was performed. Data collected included age at the time of diagnosis, slit lamp findings, cycloplegic refraction, best-corrected visual acuity, central corneal thickness, specular microscopy, and corneal topography findings whenever available. RESULTS: Twenty-seven eyes of 19 patients were included (11 unilateral and 8 bilateral cases). Ten patients were girls (52.6%). Left eye was affected in 14 eyes. The mean age at the time of diagnosis was 8.5 ± 3.3 years, with a mean follow-up of 5.3 years. In unilateral cases, there was a statistically significant difference in the endothelial cell density (P = 0.01), coefficient variation (P = 0.03), and hexagonality (P = 0.01) between the affected and the contralateral unaffected eyes. The mean best-corrected visual acuity at initial presentation was 0.8 ± 0.2 compared with 0.9 ± 0.08 in unaffected eyes (P = 0.04). The mean astigmatism was higher in the affected eye (+1.7 diopters) compared with (+1.00) the unaffected eye (P = 0.07). At initial presentation, 7 of 27 eyes had amblyopia, which resolved, either partially or completely, in 5 eyes after treatment. CONCLUSIONS: PPCD can present early in children with astigmatism and anisometropic amblyopia. A careful slit lamp examination for children presenting with anisoastigmatism is necessary to diagnose PPCD. Contrary to adults, presentation is often unilateral. Such patients should be followed up regularly with cycloplegic retinoscopy to prevent and treat refractive amblyopia if present.
Buch KA, Bouffard MA, Kardon RH, Wills A-MA, Privitera CM, Sharma M, Wray SH. Clinical Correlation Between Vertical Gaze Palsy and Midbrain Volume in Progressive Supranuclear Palsy. J Neuroophthalmol 2022;42(2):246-250.Abstract
BACKGROUND: Supranuclear vertical gaze palsies and slowed vertical saccades are characteristic clinic features of progressive supranuclear palsy (PSP). The "hummingbird sign," reflective of midbrain atrophy, is a classic radiographic sign of PSP. Correlation between eye movement abnormalities and radiographic findings in PSP has been reported previously. However, due to the use of clinical criteria not commonly employed in neuro-ophthalmic practice and neuroimaging techniques that are not widely available, it remains unclear whether correlation between midbrain structure and characteristic ocular-motor disturbances can be helpful to neuro-ophthalmologists seeking to adjudicate difficult or unusual diagnostic cases. METHODS: Patients with a diagnosis of probable PSP according to Movement Disorders Society criteria were studied retrospectively. A neuroradiologist calculated brainstem volumes in enrolled participants and normal controls. Spearman correlations were used to correlate the extent of eye movement limitation as assessed by 2 neuro-ophthalmologists with brainstem volumes. RESULTS: Fourteen participants with PSP and 15 healthy controls with similar age and gender distribution were enrolled and evaluated retrospectively. All 14 participants with PSP had undergone MRIs. Midbrain atrophy significantly correlated with the PSP rating scale (P < 0.001). PSP patients had significantly reduced volumes in the midbrain (P -0.0026), tegmentum (0.0001), tectum (0.0001), and medulla (P = 0.0024) compared with normal controls. Notes documenting quantified ocular motor function were available in 7 of 14 participants with PSP. Midbrain atrophy significantly correlated with in the extent of upward gaze limitation (P = 0.03). CONCLUSIONS: The severity of upward gaze limitation correlates with the severity of midbrain atrophy in patients with PSP. Recognition of this correlation may help to adjudicate diagnostic dilemmas and guide further evaluation.
Danford ID, Scruggs BA, Capone A, Trese MT, Drenser KA, Thanos A, Nudleman E, Amphornphruet A, Tipsuriyaporn B, Hubbard BG, Ells A, Harper AC, Goldstein J, Calvo C, Wallace-Carrete C, Berry D, Chang E, Leishman L, Shapiro M, Blair M, Mikhail M, Shields CL, Schwendeman R, Yonekawa Y, Gupta MP, Orlin A, Prakhunhungsit S, Mukai S, Berrocal A, Hartnett EM, Campbell PJ. The Prevalence of Retinal Disease and Associated CNS Disease in Young Patients with Incontinentia Pigmenti. Ophthalmol Retina 2022;6(12):1113-1121.Abstract
PURPOSE: To evaluate the prevalence of retinal disease on fluorescein angiography (FA) in patients with incontinentia pigmenti (IP) and to compare the severity of retinal disease in those with and without known central nervous system (CNS) disease. DESIGN: Multi-institutional consecutive retrospective case series. SUBJECTS: New patients with a diagnosis of IP were seen at the Casey Eye Institute at the Oregon Health and Science University (OHSU), Moran Eye Center, University of Utah, or Bascom Palmer Eye Institute, University of Miami from December 2011 to September 2018. METHODS: Detailed ophthalmoscopic examination and FA were recommended for all new patients and performed on every patient who had parental consent. Ophthalmoscopic findings and FA images were graded for severity by 2 masked graders on a 3-point scale: 0 = no disease, 1 = vascular abnormalities without leakage, 2 = leakage or neovascularization, and 3 = retinal detachment. The presence of known CNS disease was documented. Additional cases were obtained from a pediatric retina listserv for examples of phenotypic variation. MAIN OUTCOME MEASURES: The proportion of eyes noted to have disease on ophthalmoscopy compared with FA and the severity of retinal disease in those with and without known CNS disease. RESULTS: Retinal pathology was detected in 18 of 35 patients (51%) by indirect ophthalmoscopy and 26 of 35 patients (74%) by FA (P = 0.048) in a predominantly pediatric population (median age, 9 months). Ten patients (29%) had known CNS disease at the time of the eye examination. A Wilcoxon rank-sum test indicated that the retinal severity scores for patients with CNS disease (median, 2) were significantly higher than the retinal severity scores for patients without CNS disease (median, 1), z = -2.12, P = 0.034. CONCLUSIONS: Retinal disease is present in the majority of patients with IP, and ophthalmoscopic examination is less sensitive than FA for detection of disease. There may be a correlation between the severity of retinal and CNS disease.
Oke I, Lorenz B, Basiakos S, Gokyigit B, Ugo Dodd M-M, Laurent E, Hunter DG, Goberville M, Elkamshoushy A, Tsai C-B, Orge F, Velez FG, Jeddawi L, Gravier N, Li N, Shah AS, Dagi LR, Dagi LR. Nasal Transposition of the Split Lateral Rectus Muscle for Strabismus Associated With Bilateral 3rd-Nerve Palsy. Am J Ophthalmol 2022;242:165-172.Abstract
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.
Liebman DL, Tam EK, Lithgow MY, Kane JE, Fischbein NJ, Lefebvre DR, Chwalisz BK, Gaier ED. Optic Perineuritis Associated With Cryptococcal Meningitis Presenting With a "Hot Orbit" in a Patient With Chronic Lymphocytic Leukemia. J Neuroophthalmol 2022;42(2):272-277.Abstract
ABSTRACT: A 75-year-old man presented with 3 days of progressive left retro-orbital pain, eyelid swelling, tearing, and pain with extraocular movement. His medical history was significant for type II diabetes mellitus and chronic lymphocytic leukemia, stable on no therapy since diagnosis 8 years prior. The initial examination was significant for diffuse restriction of left ocular motility, marked lid edema, and mild dyschromatopsia. Computed tomography demonstrated asymmetric left periorbital soft tissue swelling and intraconal fat stranding with an irregular left optic nerve sheath complex and clear paranasal sinuses. He was hospitalized for orbital cellulitis and treated empirically with broad-spectrum intravenous antibiotics, but his visual acuity declined over the ensuing 2 days. Subsequent MRI demonstrated left-greater-than-right circumferential optic nerve sheath enhancement, and leptomeningeal enhancement. An orbital biopsy demonstrated monoclonal B-cell lymphocyte aggregation, whereas a lumbar puncture was positive for Cryptococcus antigen with subsequent demonstration of abundant Cryptococcus by Papanicolaou stain. The final diagnosis was optic perineuritis secondary to cryptococcal meningitis presenting with orbital inflammation. Although his clinical course was complicated by immune reconstitution inflammatory syndrome, symptoms and signs of optic neuropathy ultimately resolved after 1 month of intensive antifungal therapy.
Simpson FC, Islam MM, Buznyk O, Edin E, Groleau M, Kozak-Ljunggren M, Magrelli FM, AbuSamra DB, Argüeso P, Chodosh J, Liszka A, Fagerholm P, Griffith M. Electron-Beam Irradiated Recombinant Human Collagen-Phosphorylcholine Corneal Implants Retain Pro-Regeneration Capacity. Front Bioeng Biotechnol 2022;10:883977.Abstract
Sterilization of biodegradable, collagen-based implants is challenging as irradiation sterilization methods can alter their mechanical properties. Electron beam (EB) irradiation is a terminal sterilization method that has been used for biologically-derived implants. Here, recombinant human collagen type III-phosphorylcholine (RHCIII-MPC) hydrogels were irradiated with EB doses of 17, 19, or 21 kGy and their subsequent biocompatibility and ability to promote regeneration in rabbit corneas was evaluated. Unirradiated hydrogels stored in 1% chloroform in phosphate-buffered saline (C-PBS) were the controls. There were no significant differences between irradiated and non-irradiated samples in optical or physical properties (tensile strength, modulus, elasticity), or the ability to support cell growth. However, irradiated implants were more sensitive to high levels of collagenase than unirradiated controls and the C-PBS implants had increased cell growth compared to EB and controls at 72 h. Corneal implants e-beamed at 17 kGy or e-beamed and subsequently frozen (EB-F) to increase shelf-life showed no adverse biological effects of the irradiation. EB, EB-F, and C-PBS implanted corneas all rapidly re-epithelialized but showed mild neovascularization that resolved over 6 months. The regenerated neo-corneas were transparent at 6 months post-operation. In vivo confocal microscopy confirmed normal morphology for the epithelium, stroma, sub-basal nerves and unoperated endothelium. Histology showed that all the regenerated corneas were morphologically similar to the normal. Immunohistochemistry indicated the presence of a differentiated corneal epithelium and functional tear film. In conclusion, the e-beamed corneal implants performed as well as non-irradiated control implants, resulting in fully regenerated neo-corneas with new nerves and without blood vessels or inflammation that may impede vision or corneal function. Therefore, a complete validation study to establish EB irradiation as an effective means for corneal implant sterilization prior to clinical application is necessary as a next step.
Littau JL, Velilla L, Hase Y, Villalba-Moreno ND, Hagel C, Drexler D, Osorio Restrepo S, Villegas A, Lopera F, Vargas S, Glatzel M, Krasemann S, Quiroz YT, Arboleda-Velasquez JF, Kalaria R, Sepulveda-Falla D. Evidence of beta amyloid independent small vessel disease in familial Alzheimer's disease. Brain Pathol 2022;32(6):e13097.Abstract
We studied small vessel disease (SVD) pathology in Familial Alzheimer's disease (FAD) subjects carrying the presenilin 1 (PSEN1) p.Glu280Ala mutation in comparison to those with sporadic Alzheimer's disease (SAD) as a positive control for Alzheimer's pathology and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) bearing different NOTCH3 mutations, as positive controls for SVD pathology. Upon magnetic resonance imaging (MRI) in life, some FAD showed mild white matter hyperintensities and no further radiologic evidence of SVD. In post-mortem studies, total SVD pathology in cortical areas and basal ganglia was similar in PSEN1 FAD and CADASIL subjects, except for the feature of arteriosclerosis which was higher in CADASIL subjects than in PSEN1 FAD subjects. Further only a few SAD subjects showed a similar degree of SVD pathology as observed in CADASIL. Furthermore, we found significantly enlarged perivascular spaces in vessels devoid of cerebral amyloid angiopathy in FAD compared with SAD and CADASIL subjects. As expected, there was greater fibrinogen-positive perivascular reactivity in CADASIL but similar reactivity in PSEN1 FAD and SAD groups. Fibrinogen immunoreactivity correlated with onset age in the PSEN1 FAD cases, suggesting increased vascular permeability may contribute to cognitive decline. Additionally, we found reduced perivascular expression of PDGFRβ AQP4 in microvessels with enlarged PVS in PSEN1 FAD cases. We demonstrate that there is Aβ-independent SVD pathology in PSEN1 FAD, that was marginally lower than that in CADASIL subjects although not evident by MRI. These observations suggest presence of covert SVD even in PSEN1, contributing to disease progression. As is the case in SAD, these consequences may be preventable by early recognition and actively controlling vascular disease risk, even in familial forms of dementia.
Glonek T, Snogren T, Schmidt SY, Hearn SL, Isreb MA, Greiner JV. Phosphatic metabolism in dark- and light-adapted rat retinas. Exp Eye Res 2022;221:109141.Abstract
This study defines retinal phosphatic metabolites and their adjustment to illumination in rat retinas under conditions that preserve retinal function. Metabolic data are measured using high-performance liquid chromatography (HPLC) and 31P nuclear magnetic resonance (31P NMR) spectroscopy after 10 min of light exposure in vivo compared with retinas from dark-adapted rats. Multiple high-energy and low-energy phosphatic metabolites of intermediary metabolism were quantified. The concentration of the high-energy phosphate adenosine triphosphate (ATP) remained unchanged from dark- to light-adaptation. Under the same conditions the concentrations of the high-energy phosphates guanosine triphosphate (GTP) and creatine phosphate increased, whereas the inorganic phosphate decreased. Comparing dark-adapted controls with retinas light-adapted either in vitro or in vivo, the evidence is consistent with a light-dependent increase in GTP and a decrease in cyclic guanosine monophosphate. Although cyclic adenosine monophosphate (cAMP) levels were lower in retinas light-adapted in vivo than in the dark-adapted controls, this did not seem to be an effect of light, as cAMP levels decreased similarly after 10 min incubation in dark or light in parallel with recovery of ATP/adenosine diphosphate ratios. This study: (1) reports on retinal metabolic changes with adjustment in illumination, (2) provides baseline measurements of retinal phosphatic metabolites in whole retinas, and (3) reports on the validity of chromatographic and spectroscopic methods used for studying retinal metabolism establishing a high correlation among measurements made using HPLC and 31P NMR.
Islam MM, Chivu A, AbuSamra DB, Saha A, Chowdhuri S, Pramanik B, Dohlman CH, Das D, Argüeso P, Rajaiya J, Patra HK, Chodosh J. Crosslinker-free collagen gelation for corneal regeneration. Sci Rep 2022;12(1):9108.Abstract
Development of an artificial cornea can potentially fulfil the demand of donor corneas for transplantation as the number of donors is far less than needed to treat corneal blindness. Collagen-based artificial corneas stand out as a regenerative option, having promising clinical outcomes. Collagen crosslinked with chemical crosslinkers which modify the parent functional groups of collagen. However, crosslinkers are usually cytotoxic, so crosslinkers need to be removed from implants completely before application in humans. In addition, crosslinked products are mechanically weak and susceptible to enzymatic degradation. We developed a crosslinker free supramolecular gelation strategy using pyrene conjugated dipeptide amphiphile (PyKC) consisting of lysine and cysteine; in which collagen molecules are intertwined inside the PyKC network without any functional group modification of the collagen. The newly developed collagen implants (Coll-PyKC) are optically transparent and can effectively block UV light, are mechanically and enzymatically stable, and can be sutured. The Coll-PyKC implants support the growth and function of all corneal cells, trigger anti-inflammatory differentiation while suppressing the pro-inflammatory differentiation of human monocytes. Coll-PyKC implants can restrict human adenovirus propagation. Therefore, this crosslinker-free strategy can be used for the repair, healing, and regeneration of the cornea, and potentially other damaged organs of the body.
Tandias R, Lemire CA, Palvadi K, Arroyo JG. POSTERIOR VITREOUS DETACHMENT STATUS AS A PREDICTIVE FACTOR FOR OUTCOMES OF VITRECTOMY FOR DIABETIC VITREOUS HEMORRHAGE. Retina 2022;42(6):1103-1110.Abstract
PURPOSE: The purpose of this study was to evaluate the prognostic utility of the degree of vitreous attachment for predicting outcomes of vitrectomy for nonclearing vitreous hemorrhage associated with proliferative diabetic retinopathy. METHODS: Medical records of patients who underwent primary vitrectomy for dense nonclearing vitreous hemorrhage secondary to proliferative diabetic retinopathy were examined retrospectively. Eyes were divided into four groups based on the intraoperatively assessed stage of posterior vitreous detachment (PVD), ranging from Stage 0/1 (complete or near-complete vitreoretinal adhesion) to Stage 4 (complete PVD). RESULTS: Overall, 136 eyes (117 patients) were included. In comparison with eyes with a partial or complete PVD (Stages 2-4), eyes with no PVD (Stage 0/1) had a higher incidence of postoperative hypotony (8%, P = 0.03) and traction retinal detachment (27%, P = 0.002), an increased rate of repeat vitrectomy (49%, P = 0.04), and poorer best-corrected visual acuity at 6 months and 1 year postoperatively (P = 0.04 and P = 0.01, respectively). Presence of a complete PVD at baseline was independently associated with improved postoperative vision at 6 months (P = 0.04). CONCLUSION: More extensive vitreoretinal adhesion is associated with higher rates of reoperation and poorer visual outcomes after vitrectomy for dense nonclearing vitreous hemorrhage associated with proliferative diabetic retinopathy. Preoperative determination of PVD status using B-scan ultrasonography may be useful for predicting anatomical and functional outcomes after vitrectomy in these patients.

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