Chronic Hyperglycemia Compromises Mitochondrial Function in Corneal Epithelial Cells: Implications for the Diabetic Cornea.

Mitochondrial dysfunction is a major pathophysiological event leading to the onset of diabetic complications. This study investigated the temporal effects of hyperglycemia on mitochondrial metabolism in corneal epithelial cells. To accomplish this, human telomerase-immortalized corneal epithelial cells were cultured in a defined growth medium containing 6 mM glucose. To simulate hyperglycemia, cells were cultured in a medium containing 25 mM D-glucose, and control cells were cultured in mannitol. Using metabolic flux analysis, there was a hyperosmolar-mediated increase in mitochondrial respiration after 24 h. By day 5, there was a decrease in spare respiratory capacity in cells subject to high glucose that remained suppressed throughout the 14-day period. Although respiration remained high through day 9, glycolysis was decreased. Mitochondrial respiration was decreased by day 14. This was accompanied by the restoration of glycolysis to normoglycemic levels. These changes paralleled a decrease in mitochondrial polarization and cell cycle arrest. Together, these data show that chronic but not acute hyperglycemic stress leads to mitochondrial dysfunction. Moreover, the hyperglycemia-induced loss of spare respiratory capacity reduces the ability of corneal epithelial cells to respond to subsequent stress. Compromised mitochondrial function represents a previously unexplored mechanism that likely contributes to corneal complications in diabetes.

Differential effects of obstructive sleep apnea on the corneal subbasal nerve plexus and retinal nerve fiber layer.

PURPOSE: Obstructive sleep apnea (OSA) is an established independent risk factor for peripheral neuropathy. Macro and microvascular changes have been documented in OSA, including high levels of potent vasoconstrictors. In diabetes, vasoconstriction has been identified as an underlying risk factor for corneal neuropathy. This study sought to establish a potential relationship between OSA and corneal nerve morphology and sensitivity, and to determine whether changes in corneal nerves may be reflective of OSA severity. DESIGN: Single center cross-sectional study. METHODS: Sixty-seven patients were stratified into two groups: those with OSA and healthy controls. Groups were matched for age, sex, race, smoking, and dry eye status. Outcome measures included serologies, a dilated fundus exam, dry eye testing, anthropometric parameters, corneal sensitivity, subbasal nerve plexus morphology, retinal nerve fiber layer (RNFL) thickness, and the use of questionnaires to assess symptoms of dry eye disease, risk of OSA, and continuous positive airway pressure (CPAP) compliance. RESULTS: No significant differences were observed in corneal nerve morphology, sensitivity, or the number of dendritic cells. In the OSA test group, RNFL thinning was noted in the superior and inferior regions of the optic disc and peripapillary region. A greater proportion of participants in the OSA group required a subsequent evaluation for glaucoma than in the control. In those with OSA, an increase in the apnea hypopnea index was associated with an increase in optic nerve cupping. CONCLUSIONS: OSA does not exert a robust effect on corneal nerves. OSA is however, associated with thinning of the RNFL. Participants with glaucomatous optic nerve changes and risk factors for OSA should be examined as uncontrolled OSA may exacerbate glaucoma progression.

The Association Between Risk Factors for Metabolic Syndrome and Meibomian Gland Disease in a Dry Eye Cohort.

PURPOSE: Risk factors for metabolic syndrome include abdominal obesity, insulin resistance, hypertension, high triglycerides and/or low high-density lipoprotein cholesterol, and hyperglycemia. Risk factors for metabolic syndrome have been associated with dry eye disease; however, their association with meibomian gland disease (MGD), a subtype of dry eye, is unclear. In the present study, we investigated risk factors for metabolic syndrome in a dry eye cohort with and without MGD. METHODS: This retrospective case-control study evaluated electronic medical records at a major urban outpatient medical center to identify patients with a known diagnosis of dry eye disease with and without MGD. Males and females were matched for age, smoking status, race, ethnicity, and body mass index (BMI). Patient demographics, anthropometric measurements, medical history, clinical findings, and serologies were analyzed. A diagnosis of MGD was based on clinical signs noted in the medical record. RESULTS: MGD was not associated with BMI, smoking, type 2 diabetes mellitus, hypertension or hyperlipidemia in this dry eye cohort. MGD was associated with male sex and increasing age. While increasing age was weakly correlated with decreased low density lipoprotein cholesterol and non-high density lipoprotein cholesterol, serum lipid levels were not associated with MGD. CONCLUSION: Importantly, we found that risk factors for metabolic syndrome are not specifically associated with an increase in MGD when compared to non-MGD dry eye subjects. While risk factors for metabolic syndrome are associated with dry eye disease, they likely reflect a chronic systemic state of low-grade inflammation that negatively impacts the function of both lacrimal and meibomian glands.

Exenteração orbitária: série de casos / Orbital Exenteration: a series of cases

RESUMO Objetivo: Descrever os casos de exenteração orbitária de um hospital terciário brasileiro. Métodos: Estudo retrospectivo, envolvendo pacientes submetidos à exenteração orbitária no Hospital das Clínicas da Faculdade de Medicina de Botucatu, entre os anos de 1993 a 2016. As cirurgias foram realizadas sob anestesia geral, por equipe multidisciplinar composta por oftalmologistas, otorrinolaringologistas e cirurgiões de cabeça e pescoço. Resultados: Foram estudados 14 casos de exenteração orbitária, com média de idade de 63,36 ± 13,18 anos e nove homens (64,3%). Todas cirurgias foram realizadas para tratamento de tumores malignos, sendo mais frequente o carcinoma espinocelular (7 casos - 50,0%). Os sítios primários mais frequentes foram as pálpebras (50,0%), seguida pela conjuntiva (28,6%). A maioria das cirurgias foram do tipo exenteração estendida (57,1%), com cicatrização por granulação espontânea (64,3%). A sobrevida em 1 ano foi de 78,6% e em 5 anos de 71,4%. Conclusão: O carcinoma espinocelular foi a principal causa de indicação de exenteração orbitaria, sendo as pálpebras o sítio primário mais frequente. O procedimento mais realizado foi a exenteração estendida, com a grande maioria alcançando margens livres.

ABSTRACT Objective: To describe causes of orbital exenteration in a Brazilian tertiary hospital. Methods: A retrospective study was done, involving patients submitted to orbital exenteration at the Clinical Hospital of Botucatu Medical School, between the years of 1993 to 2016. The surgeries have been performed under general anesthesia, by a multidisciplinary team, composed by ophthalmologists, otolaryngologists and head and neck surgeons. Results: Fourteen cases of orbital exenteration occurred in the period of the study, with a mean age of 63.36 ± 13.18 years and nine were men (64.3%). All exenteration were due to malignant tumors, being more frequent the squamous cell carcinoma (7 cases - 50.0%). The most common primary sites were the eyelids (50.0%) followed by the conjunctiva (28.6%). The majority of the surgeries was extended exenteration type (57.1%) and most of the reconstructions was made by spontaneous granulation (64.3%). The survivor rate in 1 year was 78,6% and in 5 years was 71.4%. Conclusion: The main cause of orbital exenteration was squamous cell carcinoma and the most frequent primary site was the eyelids. Extended exenteration was necessary for the majority of cases, most of them with free margins.

Nanoskin: uso para reposição de volume na cavidade anoftálmica / Use of Nanoskin for volume replacement of the eye socket

RESUMO Objetivo: Avaliar a biocompatibilidade da Nanoskin para reposição de volume em cavidades enucleadas ou evisceradas de coelhos. Métodos: Estudo experimental, utilizando implantes de Nanoskin (Innovatecs®, São Carlos, Brasil), celulose bacteriana produzida pela bactéria Acetobacter xylinum tendo como substrato o chá-verde. Implantes de 10mm de diâmetro/5mm de espessura foram colocados em cavidades enucleadas (G1) ou evisceradas (G2) de 21 coelhos, avaliados clinicamente todos os dias, sacrificados aos 7, 30 e 90 dias após a cirurgia. O material foi removido e preparado para exame de microscopia óptica. Resultados: Sinais flogísticos discretos no pósoperatório imediato, não tendo sido evidenciados sinais infecciosos ou extrusão de nenhum implante. Houve aparente redução do volume ao longo do período experimental. Histologicamente ambos os grupos foram muito semelhantes, apresentando aos 7 dias células inflamatórias (predominantemente monócitos e neutrófilos), rede de fibrina e hemácias. A Nanoskin apresentava-se como pequenas esferas, de cor rósea, com pequenos espaços entre elas, permeados por escassas células inflamatórias. As células inflamatórias se modificaram ao longo de período experimental, sendo possível observar aos 30 dias células gigantes multinucleadas e fibroblastos maduros permeando o implante. Aos 90 dias, a estrutura do implante apresentava-se desorganizada, amorfa, com restos necróticos e com áreas ovoides, revestidas por fina membrana rósea, que pareciam se agrupar, vazias ou preenchidas por material acelular, róseo ou acinzentado. Conclusão: A Nanoskin provocou reação inflamatória que levou à reabsorção e redução do volume do implante. Novas formulações devem ser estudadas a fim de ter um produto que seja permanente para reparo da cavidade anoftálmica.

ABSTRACT Objective: The aim of this study was to evaluate the biocompatibility of Nanoskin for replacing volume in enucleated or eviscerated anophthalmic sockets of rabbits. Methods: An experimental study was carried out using enucleated or eviscerated rabbits, which received Nanoskin implants (Innovatecs®, São Carlos, Brazil), a cellulose produced by a bacteria (Acetobacter xylinum) using green tea as substrate. Implants of 10mm diameter/5mm of thickness were used placed in enucleated (G1) or eviscerated (G2) anophthalmic sockets of 21 rabbits.They were clinically examined daily, sacrificed at 7, 30 and 90 days after surgery and the material was removed and prepared for histological examination. Results: There were discrete signs of inflammation in the immediate postoperative period, with no evidence of infection or extrusion in any animal. However apparent reduction of volume during the trial period occurred. Histologically both groups were similar, with inflammatory cells (mainly monocytes and neutrophils), fibrin and hemaceas at 7 days postoperatively.The Nanoskin was presented as small pink spheres, with small gaps between them and permeated by few inflammatory cells. These cells have changed over the study, at 30 days multinucleated giant cells and mature fibroblasts that permeate the implant were observed. At 90 days, the structure of the implant was disorganized, amorphous, with necrotic debris and ovoid areas covered with thin pink membrane that seemed to cluster, empty or filled with no cellular pink or gray material. Conclusion: Nanoskin caused an inflammatory reaction leading to reabsorption and reduction of implant volume. New formulations should be studied in order to have a permanent product to repair the anophthalmic socket.