OBJECTIVE: The study investigated effectiveness of a novel PEDF peptide mimetic to alleviate dry eye-like pathologies in a Type I diabetic mouse model established using streptozotocin.
METHODS: Mice were treated topically for 3-6 weeks with Ppx (a 17-mer PEDF mimetic) 2x/day or vehicle. Corneal sensitivity, tear film, epithelial and endothelial injury were measured using Cochet-Bonnet esthesiometer, phenol red cotton thread wetting, fluorescein sodium staining, and ZO1 expression, respectively. Inflammatory and parasympathetic nerve markers and activation of the MAPK/JNK pathways in the lacrimal glands were measured.
RESULTS: Diabetic mice exhibited features of dry eye including reduced corneal sensation and tear secretion and increased corneal epithelium injury, nerve degeneration, and edema. Ppx reversed these pathologies and restored ZO1 expression and morphological integrity of the endothelium. Upregulation of IL-1β and TNFα, increased activation of P-38, JNK, and ERK, and higher levels of M3ACHR in diabetic lacrimal glands were also reversed by the peptide treatment.
CONCLUSIONS: The study demonstrates that topical application of a synthetic PEDF mimetic effectively alleviates diabetes-induced dry eye by restoring corneal sensitivity, tear secretion, and endothelial barrier and lacrimal gland function. These findings have significant implications for the potential treatment of dry eye using a cost-effective and reproducible approach with minimal invasiveness and no obvious side effects.

OBJECTIVE: To analyse and quantify ocular surface parameters in patients with unilateral neurotrophic keratitis (NK) induced by trigeminal nerve injury post-neurosurgery.
METHODS: The study included 26 unilateral NK patients who had undergone neurosurgery, and 20 matched normal controls. Demographic and clinical characteristics of all participants were collected and analysed. Slit-lamp examination, Cochet-Bonnet aesthesiometry, Keratograph 5 M, and LipiView interferometer were performed on both eyes of 17 mild NK patients. For nine moderate/severe NK patients, sub-basal nerve density was measured by in vivo confocal microscopy.
RESULTS: Of the 26 patients, nine had acoustic neuroma, nine had trigeminal neuralgia, and eight had neoplasms. Facial nerve paralysis was observed in one of the 17 mild NK eyes (5.9%) and seven of the nine moderate/severe NK eyes (77.8%). Compared to contralateral and normal control eyes, 26 NK eyes showed significantly reduced sensitivity in five corneal regions (P < 0.05). Corneal sensitivity in moderate/severe NK eyes was significantly lower than in mild NK eyes (P < 0.05). Moderate/severe NK eyes had poor visual acuity, and their sub-basal nerve density was lower than that of the controls. The onset of the moderate/severe NK was from 0.5 to 24 months (median [Q1, Q3], 1 [0.5, 2.5] months) after neurosurgery. For the mild NK eyes, the number of total blinks, the first non-invasive tear breakup time (NITBUT) and average NITBUT were significantly lower than contralateral and normal control eyes (P < 0.05), and the number of partial blinks and partial blinking rate were significantly higher than the other two control groups (P < 0.05).
CONCLUSIONS: Patients with NK induced by trigeminal nerve injury following neurosurgery had decreased corneal sensitivity to various degrees accompanied by increased partial blinks and shortened NITBUT. The severity of NK is related to the severity of the corneal sensory impairment. Facial nerve paralysis can worsen the clinical progression of NK. Trial registration Chinese Clinical Trial Registry (ChiCTR2100044068, Date of Registration: March 9, 2021).

Laser-assisted in situ keratomileusis (LASIK) is the most commonly performed laser refractive surgical technique worldwide for the treatment of myopia and myopic astigmatism. In recent years, small incision lenticule extraction (SMILE) has emerged as a promising alternative to LASIK, requiring only a single femtosecond laser to create an intrastromal lenticule, which is then removed via a small incision. The technique obviates the need for a corneal flap. A number of published studies have compared the two techniques in terms of visual, refractive and ocular surface outcomes. This review compares the clinical outcomes between LASIK and SMILE in treating myopia and myopic astigmatism based on studies published in the last 5 years. Twenty-two studies were included, all of which were observational in nature. Results suggest that the two techniques have comparable visual outcomes in terms of safety, efficacy and predictability, although recovery in visual acuity may be slower in SMILE-treated than LASIK-treated eyes. SMILE is found to result in less severe postoperative dry eye symptoms and faster recovery of corneal sensitivity than LASIK. It is important to note, however, that the SMILE technique is limited by the lack of a cyclotorsion-compensation system and option for customized treatment profile. The heterogeneity of results in this review may be attributable to the use of different LASIK platforms in different studies. Few studies compared the outcomes regarding severity of myopia. Future prospective randomized controlled trials with a larger sample size and longer follow-up period will be highly beneficial for progress in this field.

Conjunctival microvascular responses may be a surrogate metric of efferent neural pathway function innervating the ocular surface as changes in blood flow occur within seconds after a stimulus. As somatosensory dysfunction may partially underlie dry eye (DE), in this study we evaluate whether bulbar conjunctival microvascular alterations correlate with various aspects of DE.
Fifty-six DE patients were prospectively recruited from a Veterans Affairs ophthalmology clinic over an 11-month period. DE symptoms and ocular pain were assessed along with DE signs. A novel functional slit lamp biomicroscope (FSLB) was used to image the temporal bulbar conjunctiva from the right eye before and after central corneal stimulation with an air puff. Blood flow velocities were measured and noninvasive microvascular perfusion maps (nMPMs) were created.
The bulbar blood flow velocity was 0.50 ± 0.15 mm/s at baseline and increased to 0.55 ± 0.17 mm/s after stimulation (P < 0.001); the average change in velocity was 0.05 ± 0.09. nMPMs values and venule diameter, on the other hand, did not significantly increase after stimulation (1.64 ± 0.004 at baseline, 1.65 ± 0.04 after stimulation, P = 0.22 and 22.13 ± 1.84 μm at baseline, 22.21 ± 2.04 μm after stimulation, P = 0.73, respectively). Baseline blood flow velocity positively associated with Schirmer scores (r = 0.40, P = 0.002). Those with higher self-rated wind hyperalgesia demonstrated less change in blood flow velocity (r = -0.268, P = 0.046) after air stimulation on the central cornea.
Conjunctival blood flow velocity, but not vessel diameter or complexity, increases after wind stimuli. Baseline flow positively correlated with Schirmer scores while change in flow negatively correlated with self-reported wind hyperalgesia.

OBJECTIVE: The most likely etiology of post-LASIK dry eye is corneal nerve damage; however, no direct relationship between post-LASIK dry eye symptoms and nerve damage has been established, and limited information is available about the relationship between dry eye signs and corneal reinnervation after LASIK. Tear neuropeptides (SP and CGRP) are important in the maintenance of corneal nerve health, but the impact of LASIK has not yet been studied. This study evaluated changes in nerve morphology, tear neuropeptide, and dry eye, so as to establish the relationship between reinnervation and dry eye and to assess the role of tear neuropeptides in reinnervation post-LASIK.
METHODS: Twenty non-dry eye volunteers who had undergone bilateral myopic-LASIK completed this study. Corneal nerve morphology (density, width, interconnections, and tortuosity), SP and CGRP concentration, and dry eye were monitored over time prior to, 1 day, 1 week, 1, 3, and 6 months post-LASIK.
RESULTS: Dry eye symptoms and tear function, except for osmolarity (P = 0.003), remained unchanged post-LASIK. Corneal nerve morphology decreased immediately, and did not return to preoperative levels by 6 months post-LASIK (P < 0.001). Increased tear SP concentration was observed 3 months post-LASIK (P < 0.001). Associations between reinnervation as measured by increased density and lower tear SP (P = 0.03), and between increased density and decreased dry eye symptoms (P = 0.01) were found post-LASIK.
CONCLUSIONS: An inverse relationship between reinnervation post-LASIK and dry eye symptoms was found, confirming that post-LASIK dry eye is a neuropathic disease. This study is the first to demonstrate an association between tear SP and post-LASIK reinnervation, suggesting that strategies for manipulating neuropeptide concentration to improve reinnervation may improve ocular comfort post-LASIK.

OBJECTIVE: To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy (PDR), an advanced stage of diabetic retinopathy (DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal microscopy.
METHODS: Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR (NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I Test, and corneal fluorescein staining. The non-invasive tear film break-up time (NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal microscopy.
RESULTS: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls (P< 0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls (P < 0.001). Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover, significant decrease in the corneal epithelial density and morphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients.
CONCLUSIONS: Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores, and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate with the duration of diabetes. Therefore, ocular surface of the patients with PDR should be examined regularly by conventional approaches and confocal microscopy to facilitate early diagnosis and treatment of keratopathy.

To perform a comprehensive evaluation and comparison of tear function in diabetic and non-diabetic patients. Research related to tear function in diabetic and non-diabetic patients was gathered using PubMed, EBSCO, OVID. Two reviewers independently conducted the literature search. The quality assessment and the data extraction were performed in accordance with exclusion criteria and cross-checking. RevMan 5.1.7 software was used for the meta-analysis. The tear film break-up time was studied in eight articles with a total of 1449 samples. Through a random-effects model analysis, the combined weighted mean difference (WMD) was -4.44 [-5.87, -3.01]. The time in diabetic patients was shorter than that in the non-diabetic group (p < 0.00001). The basal tear secretion test was studied in seven articles with a total of 949 samples. The combined WMD was -3.96 [-5.70, -2.23], and the difference between the diabetic group and control group was statistically significant (p < 0.00001). The total tear secretion test was studied in five articles with a total of 921 samples. The combined WMD was -3.96 [-7.43, -0.50]. The difference between the diabetic and control groups was statistically significant (p = 0.03). The corneal sensitivity was compared in eight studies with a total of 976 samples. Through a random-effects model analysis, the standardized mean difference (SMD) was -5.14 [-6.99, -3.29]. The corneal sensitivity was lower in diabetic patients than the control group (p < 0.00001). Our study suggests that the tear functions are worse in diabetic patients compared with the control group. Moreover, patients with PDR are more predisposed to impaired tear functions.