Table 1.

Summary of principal studies evaluating the effect of melatonin for the treatment of different ocular pathologies.

Ocular Pathology	Reference	Compound	Target	Results
Dry eye	Navarro Gil et al. [79]	Melatonin and analogs (Agomelatine, IIK7, and 5-MCA-NAT)	Rabbits	The topical instillation of analogs of melatonin increased tears secretion: 39% with agomelatine (MT2 receptor), 28% with IIK7 (MT2 receptor), and 20% with 5-MCA-NAT (unknown receptors). Conversely, there were no changes with the melatonin.
	Hoyle et al. [80]	Ap4A + Melatonin	Rabbits	The topical instillation of Ap4A increased tear secretion by 10%, while melatonin showed no effect. The synergic effect of both molecules increased tear secretion by 34%.
Corneal wound healing	Crooke et al. [47]	Melatonin and analogs (IIK7 and 5-MCA-NAT)	Rabbits	The topical instillation of melatonin and IIK7 improved rate of corneal healing by around 47%, while 5-MCA-NAT showed no effect. This effect is mediated by the MT2 receptor, which is present in corneal epithelial cells.
	Crespo-Moral et al. [81]	Melatonin	Ex vivo Porcine eyeball	The topical exposition of melatonin in an ex vivo corneal-wound model accelerated the healing process. Notably, 60 µg/mL melatonin accelerated the healing rate during 48 h and 90 µg/mL melatonin during 72 h. Unexpectedly, 120 µg/mL melatonin decreased the healing rate after 96 h.
Myopia	Wang et al. [82]	Blue light	Guinea pigs	The retinal stimulation with blue light (480 nm) reduced eye growth, which was related to stimulate synthesis of melanopsin in retina and sclera, and to reduce both synthesis of MT1 receptor and production of melatonin in pineal gland.
	Zheng et al. [83]	AA92593 (melanopsin antagonist)	Guinea pigs	The retinal melanopsin inhibition by intravitreal injection of an antagonist AA92593 increased both the eye growth and melatonin levels in the retina, these variables being directly correlated (r = 0.74).
Cataracts	Different authors [84,85,86,87,88,89,90]	Melatonin	Rats	The use of melatonin in rat models reduced lipid peroxidation and promoted both the synthesis of glutathione and antioxidative activity of different enzymes, leading to a reduction in cataract formation.
	Pintor et al. [91]	Yellow light and AA92593	Rabbits	The inhibition of melanopsin present in the lens epithelium with a yellow filter (absorbance between 465-480 nm) and its antagonist AA92593 reduced the concentration of ATP in the aqueous humour.
Retinal damage	Liang et al. [92]	Melatonin	Mice	The muscular injection of melatonin reduced damage of photoreceptors and their apoptosis in a retinal degeneration model.
	Kaur et al. [93]	Melatonin	Rats	The intraperitoneal injection of melatonin reduced levels of VEGF, nitrite, and melatonin in the retina of hypoxic rats, also reducing retinal vascular permeability.
Age-related macular degeneration	Dieguez et al. [94]	Melatonin	Mice	The antioxidant effect of subcutaneous implantation of a pellet of melatonin helped to preserve visual function and retinal structures in a non-exudative AMD model.
	Yi et al. [95]	Melatonin	Humans	In this case series study, the daily oral administration of 3 mg melatonin for 3 months improved the signs of AMD in terms of retinal blood and retinal exudates in more than 90% of patients.