Damage-associated molecular patterns (DAMPs) are endogenous danger molecules released from the extracellular and intracellular space of damaged tissue or dead cells. Recent evidence indicates that DAMPs are associated with the sterile inflammation caused by aging, increased ocular pressure, high glucose, oxidative stress, ischemia, mechanical trauma, stress, or environmental conditions, in retinal diseases. DAMPs activate the innate immune system, suggesting their role to be protective, but may promote pathological inflammation and angiogenesis in response to the chronic insult or injury. DAMPs are recognized by specialized innate immune receptors, such as receptors for advanced glycation end products (RAGE), toll-like receptors (TLRs) and the NOD-like receptor family (NLRs), and purine receptor 7 (P2X7), in systemic diseases. However, studies describing the role of DAMPs in retinal disorders are meager. Here, we extensively reviewed the role of DAMPs in retinal disorders, including endophthalmitis, uveitis, glaucoma, ocular cancer, ischemic retinopathies, diabetic retinopathy, age-related macular degeneration, rhegmatogenous retinal detachment, proliferative vitreoretinopathy, and inherited retinal disorders. Finally, we discussed DAMPs as biomarkers, therapeutic targets, and therapeutic agents for retinal disorders.

Retinal diseases are one of the leading causes of blindness globally. The mainstay treatments for these blinding diseases are laser photocoagulation, vitrectomy, and repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) or steroids. Unfortunately, these therapies are associated with ocular complications like inflammation, elevated intraocular pressure, retinal detachment, endophthalmitis, and vitreous hemorrhage. Recent advances in nanomedicine seek to curtail these limitations, overcoming ocular barriers by developing non-invasive or minimally invasive delivery modalities. These modalities include delivering therapeutics to specific cellular targets in the retina, providing sustained delivery of drugs to avoid repeated intravitreal injections, and acting as a scaffold for neural tissue regeneration. These next-generation nanomedicine approaches could potentially revolutionize the treatment landscape of retinal diseases. This review describes the availability and limitations of current treatment strategies and highlights insights into the advancement of future approaches using next-generation nanomedicines to manage retinal diseases.

Purpose of review: As artificial intelligence continues to develop new applications in ophthalmic image recognition, we provide here an introduction for ophthalmologists and a primer on the mechanisms of deep learning systems. Recent findings: Deep learning has lent itself to the automated interpretation of various retinal imaging modalities, including fundus photography and optical coherence tomography. Convolutional neural networks (CNN) represent the primary class of deep neural networks applied to these image analyses. These have been configured to aid in the detection of diabetes retinopathy, AMD, retinal detachment, glaucoma, and ROP, among other ocular disorders. Predictive models for retinal disease prognosis and treatment are also being validated. Summary: Deep learning systems have begun to demonstrate a reliable level of diagnostic accuracy equal or better to human graders for narrow image recognition tasks. However, challenges regarding the use of deep learning systems in ophthalmology remain. These include trust of unsupervised learning systems and the limited ability to recognize broad ranges of disorders.

Diabetic retinopathy (DR) is a microvascular complication of diabetes in the retina. Chronic hyperglycemia damages retinal microvasculature embedded into the extracellular matrix (ECM), causing fluid leakage and ischemic retinal neovascularization. Current treatment strategies include intravitreal anti-vascular endothelial growth factor (VEGF) or steroidal injections, laser photocoagulation, or vitrectomy in severe cases. However, treatment may require multiple modalities or repeat treatments due to variable response. Though DR management has achieved great success, improved, long-lasting, and predictable treatments are needed, including new biomarkers and therapeutic approaches. Small-leucine rich proteoglycans, such as decorin, constitute an integral component of retinal endothelial ECM. Therefore, any damage to microvasculature can trigger its antifibrotic and antiangiogenic response against retinal vascular pathologies, including DR. We conducted a cross-sectional study to examine the association between aqueous humor (AH) decorin levels, if any, and severity of DR. A total of 82 subjects (26 control, 56 DR) were recruited. AH was collected and decorin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Decorin was significantly increased in the AH of DR subjects compared to controls (p = 0.0034). AH decorin levels were increased in severe DR groups in ETDRS and Gloucestershire classifications. Decorin concentrations also displayed a significant association with visual acuity (LogMAR) measurements. In conclusion, aqueous humor decorin concentrations were found elevated in DR subjects, possibly due to a compensatory response to the retinal microvascular changes during hyperglycemia.

Purpose: To observe the incidence of and risk factors for cystoid macular edema (CME) after silicone oil (SO) implantation after pars plana vitrectomy (PPV) for retinal detachment (RD) repair. Methods: This retrospective analysis used the TriNetX database to identify patients who received SO tamponade after PPV for RD between March 2014 and March 2023. The onset and regression of CME were identified using spectral-domain optical coherence tomography. The demographics, intraoperative parameters, and postoperative disease course of patients with and patients without CME were compared using χ ² tests, Student t tests, and logistic regression models. Results: Twenty (25.3%) of 79 eyes developed CME after intraocular insertion of SO. The use of 1000 cs SO (n = 50) vs 5000 cs SO (n = 29) was significantly associated with CME onset (odds ratio, 4.46; P < .05). The mean (± SD) SO tamponade duration was 199.0 ± 125.5 days. The mean time from SO implantation to detection of CME was 82.6 ± 57.9 days. Disease regression occurred in 15 (75.0%) of the 20 eyes with CME and was recorded a mean of 218.2 ± 256.2 days after SO removal. Compared with untreated groups, the frequency of CME regression was not influenced by the administration of sub-Tenon triamcinolone acetonide (75.0% vs 75.0%; P = 1.00), prednisolone acetate eyedrops (75.0% vs 75.0%; P = 1.00), or ketorolac eyedrops (71.4% vs 76.9%; P = .79). Conclusions: The viscosity of the SO used for vitreous tamponade in RD repair may play a role in the development of CME, with lighter grade oil increasing the risk for disease. Furthermore, SO removal alone potentially leads to a prominent reduction in CME in most cases.