The topical administration of medicines is the preferred route in ocular therapy, at least for the anterior segment of the eye. However, the eye’s inherent functional and biological barriers all work against the active pharmaceutical ingredient (API) to efficiently reach the targeted retinal structures. The main objective of this article is to offer a systematic review of the scientific literature in recent years, focusing on the latest developments of topical treatment intended for retinal degenerative diseases. Database search returned 102 clinical studies, focused on topical treatment for age macular degeneration, macular edemas (in diabetic retinopathy, surgery related or in retinal dystrophies) or glaucoma. After the exclusion of low-powered studies and those combining vitreo-retinal surgery, 35 articles remained for analysis. Currently, the topical treatment of retinal degenerative diseases is limited by the difficulty to deliver effective drug concentrations to the posterior eye structures. However, in the case of drug classes like NSAIDs, the presence of certain molecular and metabolic features for specific representatives makes the topical administration currently feasible in several clinical contexts. For other drug classes, either a fine-tuning of the API’s pharmacokinetic profile or the use of more advanced formulation strategies, such as rationally designed nanostructured drugs and vehicles, crystalline polymorphs or supramolecular complexes, could bring the much awaited breakthrough for a more predictable and controlled delivery towards the retinal structures and could eventually be employed in the future for the development of more effective ways of delivering drugs to the posterior eye, with the ultimate goal of improving their clinical efficacy.

The future of eye reconstruction invariably includes stem cells transplantation. Corneal limbus, corneal stroma, trabeculum, retinal cells, optic nerve, and all structures that are irreversibly damaged and have no means to be repaired or replaced, through conventional treatment or surgery, represent targets for stem cell reconstruction. This review tries to answer the question if there is any clinical validation for stem therapies, so far, starting from the cornea and, on the path of light, arriving to the retina. The investigation covers the last 10 years of publications. From 2385 published sources, we found 56 clinical studies matching inclusion criteria, 39 involving cornea, and 17 involving retina. So far, corneal epithelial reconstruction seems well validated clinically. Enough clinical data are collected to allow some form of standardization for the stem cell transplant procedures. Cultivated limbal epithelial stem cells (CLET), simple limbal epithelial transplant (SLET), and oral mucosa transplantation are implemented worldwide. In comparison, far less patients are investigated in retinal stem reconstructions, with lower anatomical and clinical success, so far. Intravitreal, subretinal, and suprachoroidal approach for retinal stem therapies face specific challenges.

Neurotrophic keratopathy (NK) is a rare degenerative disease caused by trigeminal nerve impairment, leading to corneal anesthesia, epithelial breakdown, and progressive vision loss. NK produces damage through the lack of pain. Conventional treatments focus on symptom management and preventing complications but do not address the underlying nerve dysfunction. Corneal neurotization (NT) has emerged as a promising surgical intervention aimed at restoring corneal sensation and improving ocular surface homeostasis. This review examines the outcomes of corneal neurotization in NK patients, while also comparing the effectiveness of direct (DNT) and indirect (INT) techniques. Studies report significant improvement in corneal sensitivity, with success rates ranging from 60.7% to 100% (average ~90%). Most patients showed corneal sensation recovery, as measured by the Cochet–Bonnet aesthesiometer. No significant differences were found between DNT and INT outcomes. Indirect neurotization with a sural nerve graft was the most performed procedure (63% of cases), with acellular allografts demonstrating comparable efficacy while simplifying the technique. Postoperative corneal sensitivity improved significantly from a preoperative average of 2.717 mm to 36.01 mm, with reinnervation occurring within 4–6 months and peaking at 12 months. In vivo confocal microscopy confirmed nerve regeneration. Neurotization was safe, with minimal donor-site complications, typically resolving within one year. While corneal neurotization enhances corneal sensation and tear film stability, visual acuity outcomes remain variable, influenced by pre-existing corneal damage. Early intervention is recommended to prevent irreversible scarring. Further studies with larger sample sizes are needed to refine surgical techniques and optimize patient selection, ensuring the best possible outcomes for NK patients.