Ocular surface complications of local anticancer drugs for treatment of ocular tumors.

Local chemotherapy is increasingly used, either in combination with surgery or as monotherapy, for management of ocular tumors. Yet many of the local chemotherapeutic agents used for ocular tumors are cytotoxic drugs that are frequently associated with toxicities in normal ocular tissues. Understanding and managing these side effects are important because they affect treatment tolerability, outcome and quality of vision. Herein, we review local anticancer drugs administered for the treatment of ocular tumors, with an emphasis on their toxicities to the ocular surface, adnexa and lacrimal drainage system. We provide the underlying mechanisms and management strategies for the ocular side effects. Recent innovations in anticancer immunotherapy and ocular drug delivery systems also are discussed as new potential therapeutic modalities for alleviation of side effects.

Effect of IRT5 probiotics on dry eye in the experimental dry eye mouse model.

OBJECTIVE: To investigate the clinical effects of IRT5 probiotics in the environmental dry eye model. METHODS: Eight week old male C57BL/6 mice were randomly divided into two groups; control group (n = 16) received oral gavage of 300 µL phosphate-buffered saline (PBS) alone once daily, IRT5 group (n = 9) received oral gavage of 1 x 109 CFU IRT5 probiotics powder in 300 µL PBS once daily, both groups for 11 to 12 days. Simultaneously, all mice underwent dry eye induction. Tear secretion, corneal staining and conjunctival goblet cell density were evaluated. Quantative real-time polymerase chain reaction (RT-PCR) for inflammation-related markers was performed. 16S ribosomal RNA of fecal microbiome was analyzed and compositional difference, alpha and beta diversities were assessed. RESULTS: There was no difference in NEI score but significant increase in tear secretion was observed in IRT5 group (p < 0.001). There was no significant difference in goblet cell density between groups. Quantative RT-PCR of cornea and conjunctiva revealed increased TNF-α expression in IRT5 group (p < 0.001) whereas other markers did not significantly differ from control. IRT5 group had significantly increased species diversity by Shannon index (p = 0.041). Beta diversity of genus by UniFrac principle coordinates analysis showed significant distance between groups (p = 0.001). Compositional differences between groups were observed and some were significantly associated with tear secretion. Multivariate linear regression analysis revealed Christensenellaceae (p = 0.009), Lactobacillus Helveticus group (p = 0.002) and PAC001797_s (p = 0.011) to strongly influence tear secretion. CONCLUSION: In experimental dry eye model, IRT5 probiotics treatment partially improves experimental dry eye by increasing tear secretion which was associated with and influenced by the change in intestinal microbiome. Also, intestinal microbiome may affect the lacrimal gland through a different mechanism other than regulating inflammation.

Comparative effects of various types of toric intraocular lenses on astigmatism correction.

BACKGROUND: Currently, various types of toric intraocular lenses (IOL) have been manufactured and can be divided into three types according to the location of correction component; front-toric IOL (correction on anterior IOL surface), back-toric IOL (correction on posterior IOL surface), and bi-toric IOL (correction on both anterior and posterior IOL surfaces). In this study, we aimed to investigate the effectiveness of reducing corneal astigmatism of either normal or post-penetrating keratoplasty (PKP) corneas according to the type of implanted toric IOLs. METHODS: Medical records were retrospectively reviewed in 370 patients who had undergone phacoemulsification with posterior chamber toric IOL insertion (front-toric IOL, back-toric IOL or bi-toric IOL). Subjects were divided into 2 groups; subjects who had no history of corneal disease with corneal astigmatism more than 1.00 diopters (D) (G1) and subjects who received previous PKP with all corneal sutures removed and had corneal astigmatism more than 1.25 D (G2). Preoperatively intended target from SRK/T was evaluated. Refractive astigmatism and its vector analysis (J0, J45), mean numerical error (MNE) and mean absolute error (MAE) were assessed at least a month after cataract surgery. RESULTS: Mean preoperative corneal astigmatisms were 2.2 D and 4.0 D in G1 and G2, respectively. There was significant reduction of mean postoperative refractive astigmatism to 0.89 D in G1 and to 2.33 D in G2. In G1, bi-toric IOL showed significantly more improved refractive astigmatism than back-toric IOL. In G2, no difference in refractive astigmatism according to toric IOL type was observed. While G2 showed no difference in MNE among toric IOLs, in G1, bi-toric IOL showed significant hyperopic shift compared to back-toric IOL. In both groups, there was no significant difference in MAE according to type of IOL. No postoperative complications were observed. CONCLUSION: Our study suggests that all types of toric IOL are beneficial in correcting astigmatism of normal and post-PKP corneas. Noticeably, bi-toric IOL showed significantly better results in refractive astigmatism than back-toric IOL in normal cornea. However, bi-toric IOL showed a more hyperopic shift compared to back-toric IOL. Among post-PKP corneas, all types of toric IOL showed similar results.

Effects of 20% Human Serum on Corneal Epithelial Toxicity Induced by Benzalkonium Chloride: In Vitro and Clinical Studies.

PURPOSE: Benzalkonium chloride (BAK), the most commonly used preservative in ophthalmic solutions, is known to cause toxicity in the corneal epithelium. In this study, we investigated the effects of 20% human serum in cultures of BAK-damaged human corneal epithelial cells (hCECs) and in patients with toxic corneal epitheliopathy induced by BAK-containing eye drops. METHODS: hCECs were exposed to various concentrations of BAK (0%, 0.002%, 0.02%, and 0.2%) in the presence or absence of 20% human serum. After 24 hours, the metabolic activity, proliferation, apoptosis, and proinflammatory cytokine expression were evaluated in the cells. Also, cell migration was assessed using a scratch test. In the clinical study, 24 patients with toxic corneal epitheliopathy secondary to BAK-containing antiglaucoma eye drops were treated with topical application of 20% autologous serum, and corneal epithelial integrity was evaluated. RESULTS: BAK induced cytotoxicity in hCECs by inhibiting the metabolic activity, proliferation, and migration and by increasing apoptosis in a concentration-dependent manner. The level of proinflammatory cytokine IL-8 was elevated in BAK-treated cells. Addition of 20% human serum to the cultures significantly promoted the cell metabolic activity, proliferation, and migration while markedly reducing apoptosis. In line with the in vitro results, corneal punctate epithelial erosions were decreased from a National Eye Institute scale score of 4.2 ± 2.1 to 1.3 ± 1.7 in 20 of 24 patients (84%) after treatment with 20% autologous serum. CONCLUSIONS: Data demonstrate that 20% human serum is effective in treating BAK-induced cytotoxicity in hCECs and provides a basis for using 20% autologous serum for patients with preservative-induced corneal epitheliopathy.