Adenylyl Cyclase in Ocular Health and Disease: A Comprehensive Review.

Adenylyl cyclases (ACs) are a group of enzymes that convert adenosine-5'-triphosphate (ATP) to cyclic adenosine 3',5' monophosphate (cAMP), a vital and ubiquitous signalling molecule in cellular responses to hormones and neurotransmitters. There are nine transmembrane (tmAC) forms, which have been widely studied; however, the tenth, soluble AC (sAC) is less extensively characterised. The eye is one of the most metabolically active sites in the body, where sAC has been found in abundance, making it a target for novel therapeutics and biomarking. In the cornea, AC plays a role in endothelial cell function, which is vital in maintaining stromal dehydration, and therefore, clarity. In the retina, AC has been implicated in axon cell growth and survival. As these cells are irreversibly damaged in glaucoma and injury, this molecule may provide focus for future therapies. Another potential area for glaucoma management is the source of aqueous humour production, the ciliary body, where AC has also been identified. Furthering the understanding of lacrimal gland function is vital in managing dry eye disease, a common and debilitating condition. sAC has been linked to tear production and could serve as a therapeutic target. Overall, ACs are an exciting area of study in ocular health, offering multiple avenues for future medical therapies and diagnostics. This review paper explores the diverse roles of ACs in the eye and their potential as targets for innovative treatments.

The Role of Insulin-like Growth Factor (IGF) System in the Corneal Epithelium Homeostasis-From Limbal Epithelial Stem Cells to Therapeutic Applications.

The corneal epithelium, comprising three layers of cells, represents the outermost portion of the eye and functions as a vital protective barrier while concurrently serving as a critical refractive structure. Maintaining its homeostasis involves a complex regenerative process facilitated by the functions of the lacrimal gland, tear film, and corneal nerves. Crucially, limbal epithelial stem cells located in the limbus (transitional zone between the cornea and the conjunctiva) are instrumental for the corneal epithelium integrity by replenishing and renewing cells. Re-epithelialization failure results in persistent defects, often associated with various ocular conditions including diabetic keratopathy. The insulin-like growth factor (IGF) system is a sophisticated network of insulin and other proteins essential for numerous physiological processes. This review examines its role in maintaining the corneal epithelium homeostasis, with a special focus on the interplay with corneal limbal stem cells and the potential therapeutic applications of the system components.

Comparison of anatomical and functional outcomes of treating myopic choroidal neovascularization with bevacizumab or ranibizumab.

PURPOSE: To compare results of treatment with bevacizumab and ranibizumab injections in myopic choroidal neovascularization (mCNV). METHODS: Retrospective, observational case series. PARTICIPANTS: patients with mCNV treated with bevacizumab or ranibizumab injections. Best corrected visual acuity (BCVA) and central retinal thickness (CRT) on optical coherence tomography (OCT) scans were collected at baseline, after 3, 6, 12, 24 months and the last visit. MAIN OUTCOME MEASURES: mean change in BCVA and CRT. RESULTS: We included 85 eyes treated with bevacizumab and 125 eyes treated with ranibizumab. There was no difference between the groups regarding BCVA and CRT change. CNV recurrence occurred at the mean time of 66.1 ± 3.7 and 57.3 ± 6.4 months in the bevacizumab- and ranibizumab-treated eyes, respectively (p = 0.006). During the first year 6.9% eyes in the bevacizumab group vs. 27.5% in the ranibizumab group had CNV recurrence (p = 0.001). Risk factors for recurrence of CNV were baseline CNV area (aHR 1.20, 95%CI 1.0-1.32, p = 0.04), subfoveal CNV (aHR 2.13, 95% CI 1.16-3.93, p = 0.01) and ranibizumab treatment (aHR 2.31, 95% CI 1.16-3.93, p = 0.008). CONCLUSION: Eyes treated with bevacizumab and ranibizumab can achieve similar anatomical and functional improvement. CNV recurrence may occur earlier and more frequently during the first year in eyes treated with ranibizumab.

Intravitreal Antivascular Endothelial Growth Factor Treatment for Inflammatory Choroidal Neovascularization in Noninfectious Uveitis.

PURPOSE: To compare visual outcome and recurrence rates of eyes with noninfectious inflammatory choroidal neovascularization (CNV) treated with or without anti-vascular endothelial growth factor (VEGF) injections and immunosuppression. DESIGN: Retrospective, nonrandomized clinical study. METHODS: Participants: Patients with CNV secondary to noninfectious inflammatory causes who attended uveitis clinics at Moorfields Eye Hospital between January 2000 and April 2016. Data were gathered from the clinical notes of all subjects examined in clinic. MAIN OUTCOME MEASURES: change in best-corrected visual acuity (BCVA), mean time to CNV recurrence, moderate vision loss (≤20/50), and severe vision loss (≤20/200). RESULTS: A total of 166 patients (204 eyes) with noninfectious inflammatory CNV were included in this study with a median follow-up of 6.9 years (interquartile range: 2.9-11.7; 1652 eye-years). The mean BCVA at the time of CNV diagnosis was 0.38 ± 0.05 logarithm of the minimum angle of resolution (logMAR) (Snellen equivalent 20/47) in the eyes that received the first-line anti-VEGF treatment and 0.44 ± 0.03 logMAR (Snellen equivalent 20/55) in the eyes on other treatment modalities (P = .39). Eyes treated first with anti-VEGF (n = 55) received the mean of 4.35 ± 0.53 injections and showed a statistically significant improvement in vision at all time points (P < .001) except for a 5-year visit (P = .25). The rest of the eyes demonstrated no significant change in vision throughout follow-up (all P > .05). At the final visit, the mean BCVA was 0.26 ± 0.11 logMAR (Snellen equivalent 20/36) in the former and 0.35 ± 0.06 logMAR (Snellen equivalent 20/44) in the latter. The mean time to CNV recurrence was 186 ± 15.1 months, and the risk was significantly reduced by treatment with oral corticosteroids (adjusted hazard ratio = 0.32, confidence interval: 0.17-0.59, P < .001) or anti-VEGF injections (adjusted hazard ratio = 0.31, confidence interval: 0.18-0.52, P < .001). CONCLUSIONS: Eyes that developed inflammatory CNV were at risk of vision loss. Those receiving early anti-VEGF injections achieved a better visual outcome and had a reduced risk of CNV recurrence. Oral corticosteroids also had an effect that reduces the risk of recurrence in eyes previously treated.

The prognostic value of total macular external limiting membrane and ellipsoid zone damage for clinical outcome in treatment-resistant neovascular age-related macular degeneration.

PURPOSE: To examine the prognostic value of the extent of damage to the ellipsoid zone (EZ) and external limiting membrane (ELM) in response to the treatment of age-related macular degeneration (AMD) eyes switched from ranibizumab to aflibercept. METHODS: This is a retrospective study of patients with neovascular AMD resistant to ranibizumab defined as having persistent intra- or subretinal fluid on OCT scans despite at least 6-month treatment and switched to aflibercept. Clinical data was collected and quantitative measurements of the area of EZ and ELM damage were obtained, on en-face optical coherence tomography images, at the time of switch to aflibercept (baseline) and up to 6 months of follow-up. RESULTS: The study included 71 eyes (52.1% right eye) of 71 patients. At baseline, there was a correlation between the size of the EZ and ELM damaged area and BCVA (R = -0.39, p = 0.001 and R = -0.47, p < 0.001, respectively). The EZ and ELM damaged areas maintained correlation with BCVA at 6 months (R = -0.28, p = 0.01 and R = -0.39, p = 0.001, respectively). Central retinal thickness did not correlate with BCVA at the time of switch (p = 0.38) or at 6 months (p = 0.36). CONCLUSIONS: The extent of damage to the EZ and ELM correlates with BCVA following a switch in treatment.

Multi-procedure management in an eyeglasses-related open globe injury.

We present a case of successful multi-procedure management of a patient with an open globe injury. A 47-year-old man sustained an injury to his left eye caused by glass fragments of his own spectacles shattered while he was protecting an unknown woman from physical assault at a bus stop. Over a span of 65 months the patient underwent multiple procedures including primary wound repair, penetrating keratoplasty combined with extracapsular cataract extraction, neodymium: YAG laser capsulotomy, and laser-assisted subepithelial keratectomy (LASEK), and had a successfully treated episode of corneal graft rejection. This sequence of treatment substantially improved his left eye vision from hand movements at the time of admission to 0.9-0.5 × 90 at the last follow-up nearly 10 years after the trauma. Proper initial surgical management of an open globe injury can create the possibility for virtually complete vision restoration.