Metabolic and proteomic indications of diabetes progression in human aqueous humor.

Diabetes mellitus is a multiorgan systemic disease impacting numerous ocular structures that results in significant ocular morbidity and often results in more frequent corneal and glaucoma surgeries for affected individuals. We hypothesize that the systemic metabolic and proteomic derangement observed in the progression of diabetes influences the composition of the aqueous humor (AH), which ultimately impacts the anterior segment health of the eye. To identify changes associated with diabetes progression, we mapped the metabolite profile and proteome of AH samples from patients with varying severities of type II diabetes (T2DM). Patients were classified as nondiabetic (ND or control), non-insulin-dependent diabetic without advanced features of disease (NAD-ni), insulin-dependent diabetic without advanced features (NAD-i), or diabetic with advanced features (AD). AH samples collected from the anterior chamber during elective ophthalmic surgery were evaluated for metabolite and protein expression changes associated with diabetic severity via gas chromatography/mass spectrometry and ultra-high performance liquid chromatography tandem mass spectrometry, respectively. Metabolic and proteomic pathway analyses were conducted utilizing MetaboAnalyst 4.0 and Ingenuity Pathway Analysis. A total of 14 control, 12 NAD-ni, 4 NAD-I, and 14 AD samples were included for analysis. Elevated levels of several branched amino acids (e.g., valine, leucine, isoleucine), and lipid metabolites (e.g., palmitate) were found only with increasing diabetic severity (i.e., the AD group). Similar proteomic trends were noted in amino acid and fatty acid metabolism and the unfolded protein/stress response. These results represent the first report of both metabolomic and proteomic evaluation of aqueous humor. Diabetes results in metabolic and proteomic perturbations detectable in the AH, and unique changes become manifest as T2DM severity worsens. Changes in AH composition may serve as an indicator of disease severity, risk assessment of anterior segment cells and structures, and potential future therapies.

Boston type 1 keratoprosthesis for primary congenital glaucoma.

BACKGROUND/AIMS: To evaluate the Boston type 1 keratoprosthesis (KPro-1) in treatment of eyes with primary congenital glaucoma. METHODS: A retrospective review was performed of every eye with congenital glaucoma that was treated with a KPro-1 at a tertiary eye care centre between 1 January 2008 and 1 July 2014. The main outcome measures were visual outcome, prosthesis retention and postoperative complications. RESULTS: Six eyes of six patients met the inclusion criteria. This included two paediatric patients, aged 6 months and 6 years, and four adults who were 27-33 years of age. Preoperatively, the best corrected visual acuity (BCVA) was worse than 20/400 in every eye. Three eyes had hand motions and one eye had light perception vision. After a mean follow-up period of 31 months (range 16-51 months), three eyes (50.0%) had a BCVA that was ≥20/400. Overall, the BCVA improved in four eyes (66.7%), and remained the same in two eyes (33.3%). The device was retained in six eyes (83.3%). One or more complications occurred in five eyes (83.3%) and included sterile corneal ulceration (three eyes), retroprosthetic membrane formation (three eyes), progressive glaucomatous optic neuropathy (two eyes), device extrusion (one eye) and an epiretinal membrane (one eye). CONCLUSIONS: The Boston KPro-1 has an excellent prognosis for retention in eyes with congenital glaucoma. The visual prognosis remains guarded due to the high prevalence of pre-existing ocular comorbidity and the common occurrence of sight-threatening postoperative complications.