Diabetic keratopathy (DK) is a common, but underdiagnosed, ocular complication of diabetes mellitus (DM) that has a significant economic burden. It is characterised by progressive damage of corneal nerves, due to DM-induced chronic hyperglycaemia and its associated metabolic changes. With advances in corneal nerve imaging and quantitative analytic tools, studies have shown that the severity of diabetic corneal neuropathy correlates with the status of diabetic peripheral neuropathy. The corneal nerve plexus is, therefore, considered as an important surrogate marker of diabetic peripheral neuropathy and helps in the evaluation of interventional efficacy in the management of DM. The clinical manifestations of DK depend on the disease severity and vary from decreased corneal sensitivity to sight-threatening corneal infections and neurotrophic ulcers. The severity of diabetic corneal neuropathy and resultant DK determines its management plan, and a step-wise approach is generally suggested. Future work would focus on the exploration of biomarkers for diabetic corneal neuropathy, the development of new treatment for corneal nerve protection, and the improvement in the clinical assessment, as well as current imaging technique and analysis, to help clinicians detect diabetic corneal neuropathy earlier and monitor the sub-clinical progression more reliably.

Allergic conjunctivitis is one of the most common external eye diseases and the prevalence has been increasing. The mainstay of treatment is topical eye drops. However, low bioavailability, low ocular drug penetration, transient resident time on the ocular surface due to tear turnover, frequent topical applications and dependence on patient compliance, are the main drawbacks associated with topical administration. Nanotechnology-based medicine has emerged to circumvent these limitations, by encapsulating the drugs and preventing them from degradation and therefore providing sustained and controlled release. Using a nanotechnology-based approach to load the drug is particularly useful for the delivery of hydrophobic drugs such as immunomodulatory agents, which are commonly used in allergic conjunctival diseases. In this review, different nanotechnology-based drug delivery systems, including nanoemulsions, liposomes, nanomicelles, nanosuspension, polymeric and lipid nanoparticles, and their potential ophthalmic applications, as well as advantages and disadvantages, are discussed. We also summarize the results of present studies on the loading of immunomodulators or nonsteroidal anti-inflammatory drugs to nano-scaled drug delivery systems. For future potential clinical use, research should focus on the optimization of drug delivery designs that provide adequate and effective doses with safe and satisfactory pharmacokinetic and pharmaco-toxic profiles.

Keratoconus is the most common primary corneal ectasia characterized by progressive focal thinning. Patients experience increased irregular astigmatism, decreased visual acuity and corneal sensitivity. Corneal collagen crosslinking (CXL), a minimally invasive procedure, is effective in halting disease progression. Historically, keratoconus research was confined to ex vivo settings. In vivo confocal microscopy (IVCM) has been used to examine the corneal microstructure clinically. In this review, we discuss keratoconus cellular changes evaluated by IVCM before and after CXL. Cellular changes before CXL include decreased keratocyte and nerve densities, disorganized subbasal nerves with thickening, increased nerve tortuosity and shortened nerve fibre length. Repopulation of keratocytes occurs up to 1 year post procedure. IVCM also correlates corneal nerve status to functional corneal sensitivity. Immediately after CXL, there is reduced nerve density and keratocyte absence due to mechanical removal of the epithelium and CXL effect. Nerve regeneration begins after 1 month, with nerve fibre densities recovering to pre-operative levels between 6 months to 1 year and remains stable up to 5 years. Nerves remain tortuous and nerve densities are reduced. Corneal sensitivity is reduced immediately postoperatively but recovers with nerve regeneration. Our article provides comprehensive review on the use of IVCM imaging in keratoconus patients.