Limitations and advances in new treatments and future perspectives of corneal blindness / Limitações e avanços em novos tratamentos e perspectivas futuras na cegueira corneal

ABSTRACT This review is intended to describe the therapeutic approaches for corneal blindness, detailing the steps and elements involved in corneal wound healing. It also presents the limitations of the actual surgical and pharmacological strategies used to restore and maintain corneal transparency in terms of long-term survival and geographic coverage. In addition, we critically review the perspectives of anabolic agents, including vitamin A, hormones, growth factors, and novel promitotic and anti-inflammatory modulators, to assist corneal wound healing. We discuss the studies involving nanotechnology, gene therapy, and tissue reengineering as potential future strategies to work solely or in combination with corneal surgery to prevent or revert corneal blindness.(AU)

RESUMO O presente trabalho traz uma revisão das abordagens terapêuticas para a cegueira da córnea. O estudo detalha as etapas e os elementos envolvidos na cicatrização da córnea. Ele mostra as limitações das estratégias cirúrgicas e farmacológicas usadas para restaurar e manter a transparência da córnea em termos de sobrevida a longo prazo e alcance geográfico. As perspectivas dos agentes anabólicos, incluindo vitamina A, hormônios, fatores de crescimento e novos moduladores pró-mitóticos e anti-inflamatórios para auxiliar a cicatrização da ferida na córnea, são revisadas criticamente. Aqui, apresentamos estudos envolvendo nanotecnologia, terapia gênica e reengenharia de tecidos como possíveis estratégias futuras para atuar de maneira isolada ou combinada com a cirurgia da córnea para prevenir ou reverter a cegueira corneana.(AU)

Protective effects of citicoline-containing eye drops against UVB-Induced corneal oxidative damage in a rat model.

It has been reported that citicoline increases antioxidant activity in some tissues. However, the effect of citicoline on corneal wound-healing has not yet been demonstrated. The aim was to investigate the protective effects of citicoline on ultraviolet B (UVB) radiation-induced corneal oxidative damage in a rat model. Four groups (eight animals each) were investigated: controls; UVB only; UVB/citicoline; and citicoline only. Corneal oxidative damage was induced by exposure to UVB radiation at 560 µW/cm2 for five days in the UVB-exposed groups and 1% citicoline eye drops were applied (3xday) for eight days in the two citicoline groups. Corneal surface damage was evaluated by opacity and fluorescein staining. Corneal injury was assessed biochemically by measuring the concentrations of glutathione (GSH) and malondialdehyde (MDA) and the activity of corneal superoxide dismutase (SOD) and catalase. Matrix metalloproteinase (MMP) -2 and -9 and caspase-3 were evaluated by immunofluorescent staining and microscopic examination and by Western blot analysis. Corneal gene expression analysis was performed for vascular endothelial growth factor (VEGF), interleukin-1 beta (IL-1ß) and transforming growth factor-beta (TGF-ß). UVB radiation caused significant epithelial damage and evident opacity in the cornea, together with a local decrease in SOD, catalase and GSH activity. Corneal MDA concentrations increased with UVB exposure. The UVB/Citicoline group had significantly less corneal damage, greater SOD, catalase and GSH activity, and decreased MDA concentrations compared to the UVB only group (p < 0.05). Expression of TGF-ß, IL-1ß and VEGF was significantly lower in the citicoline/UVB group compared to the UVB group (p < 0.05). Interestingly, TGF-ß expression was lower in the citicoline only group compared with controls. Immunfluorescent staining and Western blot analysis showed increased MMP-2, -9 and caspase-3 in the UVB only group compared with the UVB/citicoline group. It was shown that citicoline treatment may be effective in suppressing oxidative stress and controlling inflammation in UVB corneal injury.

Rapamycin ameliorates corneal injury after alkali burn through methylation modification in mouse TSC1 and mTOR genes.

Alkali burn to the cornea is one of the most intractable injuries to the eye due to the opacity resulting from neovascularization (NV) and fibrosis. Numerous studies have focused on studying the effect of drugs on alkali-induced corneal injury in mouse, but fewer on the involvement of alkali-induced DNA methylation and the PI3K/AKT/mTOR signaling pathway in the mechanism of alkali-induced corneal injury. Thus, the aim of this study was to determine the involvement of DNA methyltransferase 3 B-madiated DNA methylation and PI3K/AKT/mTOR signaling modulation in the mechanism of alkali-induced corneal injury in a mouse model. To this end, we used bisulfite sequencing polymerase chain reaction and Western blot analysis, to study the effects of 5-aza-2'-deoxycytidine and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, which inhibit methyltransferase and PI3K respectively, on DNA methylation and expression of downstream effectors of PI3K related to corneal NV, including TSC1 and mTOR genes. The results showed that, after an intraperitoneal injection of rapamycin (2 mg/kg/day) for seven days, the alkali-induced opacity and NV were remarkably decreased mainly by suppressing the infiltration of immune cells into injured corneas, angiogenesis, VEGF expression and myofibroblasts differentiation; as well as by promoting corneal cell proliferation and PI3K/AKT/mTOR signaling. More significantly, these findings showed that epigenetic regulatory mechanisms by DNA methylation played a key role in corneal NV, including in corneal alkali burn-induced methylation modification and rapamycin-induced DNA demethylation which involved the regulation of the PI3K/AKT/mTOR signaling pathway at the protein level. The precise findings of morphological improvement and regulatory mechanisms are helpful to guide the use of rapamycin in the treatment of corneal angiogenesis induced by alkaline-burn.

Protective Effect of Vitamin C against Infancy Rat Corneal Injury Caused by Acute UVB Irradiation.

PURPOSE: Studies have shown that corneas of young children were more susceptible to Ultraviolet B (UVB) radiation damage. However, there exist limited information about the harm of UVB to eyes and preventive measures on infancy. Vitamin C as an antioxidant is widely used to prevent many diseases. Therefore, the aim of this study was to explore the protective effect of vitamin C on the cornea of infant rats with acute UVB injury. METHOD: Thirty-six infant rats were randomly divided into three groups: control (CON) group, UVB (UVB) group, and UVB+vitamin C (UVB+VitC) group. The UVB group was exposed to UVB irradiation (8 J/cm2, 15 min/d, 7 d) and the UVB+vitamin C group suffered the same UVB irradiation treated with vitamin C at the dose of 40 mg/kg via intraperitoneal injection. Then, corneal morphology was detected in vivo and in vitro at 7 d post-UVB exposure. Furthermore, serum inflammatory factors (IL-1, IL-6, and TNF-α) and oxidative status (4-HNE and MDA) were detected by ELISA, and the expression of vascular endothelial growth factor-α (VEGF-α) and superoxide dismutase (SOD) in the cornea was detected by western blot or immunofluorescent staining. RESULTS: Slit lamp detection revealed that the area of corneal desquamation and corneal neovascularization in the UVB+VitC group was significantly less than those in the UVB group at 7 d post-UVB exposure (all p < 0.05). OCT results showed that the thickness of the central cornea in the UVB+VitC group was decreased than that in the UVB group (p < 0.05). The serum inflammatory factors (IL-1, IL-6, and TNF-α) and oxidative status (4-HNE and MDA) in the UVB group were significantly increased compared with the CON group (all p < 0.05), while those factors in the UVB+VitC group were decreased compared with those in the UVB group. Furthermore, the expression of VEGF-α in the UVB+VitC group was dramatically decreased compared with that in the UVB group (p < 0.05), and the expression of SOD2 in the UVB+VitC group was dramatically increased compared with that in the UVB group at 7 d post-UVB exposure (p < 0.05). CONCLUSION: Vitamin C could protect infant rats from corneal injury induced by UVB via alleviating corneal edema, improving corneal inflammatory reaction, and decreasing VEGF-α expression.

Eye care in the intensive care unit during the COVID-19 pandemic.

Ocular complications in critical care patients are common. There has been a surge in intensive care admissions following the COVID-19 outbreak. The management of COVID-19 exposes patients to a number of specific risk factors for developing ocular complications, which include non-invasive ventilation, mechanical ventilation and prone positioning. Consequently, it is likely that there will be an increase in the number of ocular complications secondary to the management of COVID-19 patients in the intensive care unit setting, and these complications could lead to permanent visual loss and blindness. Increased awareness of eye care in the intensive care unit setting is therefore vital to help prevent visual loss and maintain quality of life for patients recovering from COVID-19.

Effects of Cisatracurium, Rocuronium, and Mivacurium on Intraocular Pressure During Induction of General Anesthesia in Ophthalmic Surgery.

OBJECTIVE: Maintaining intraocular pressure (IOP) is important in preventing ocular complications in patients undergoing ophthalmic surgery for general anesthesia. The effects of non-depolarizing neuromuscular blockers on IOP remain unclear. The present study compared the effects of cisatracurium, rocuronium, and mivacurium on IOP during induction of general anesthesia in vitreous retinal surgery. MATERIALS AND METHODS: In this prospective randomized double-blinded study, 133 patients undergoing vitreous retinal surgery were randomized into one of the three groups: Group cisatracurium (n=45), Group rocuronium (n=44), or Group mivacurium (n=44). Each drug (cisatracurium 0.1 mg kg-1 in Group cisatracurium, rocuronium 0.6 mg kg-1 in Group rocuronium, and mivacurium 0.2 mg kg-1 in Group mivacurium) was administered during induction of anesthesia. IOP and hemodynamic parameters were measured at 1 min before anesthesia induction (T0). Bispectral index (BIS) was maintained between 45 and 55 after propofol administration (T1). Train-of-four stimulation (TOF) was below 0 after muscle relaxant administration (T2) and after laryngeal mask implantation (T3). RESULTS: Both ipsi-operative and control-operative IOP at T1, T2, and T3 significantly decreased from the baseline values (T0) in all three groups (P<0.05). The IOP changes between T1 and T2 among three groups were similar (P>0.05). The values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) at T1 and T2 significantly decreased in all three groups compared to T0 (P<0.05). CONCLUSION: Bilateral IOP significantly decreased from the baseline values in all three groups during the induction phase. Cisatracurium, rocuronium, and mivacurium did not induce significant changes in bilateral IOP.

Exploring the Protective Potential of Carboxymethyl Terminalia catappa Polysaccharide on Blue Light Light-Emitting Diode Induced Corneal Damage.

BACKGROUND: Excessive blue light light-emitting diode (LED) exposure and consequent oxidative stress causes corneal damage and corneal injuries are the major problem arising these days due to excessive use of mobile phone, TV, environment pollution, etc. Objective: In the present investigation, the protectiveness of carboxymethyl Terminalia catappa (CTC) from blue light LED-induced corneal damage was explored. METHODS: For this purpose, Terminalia catappa (TC) was functionalized by carboxymethylation and its structural modification was confirmed by spectral attributes. Further, the CTC protective eye drop formulations (0.025-1%, w/v) were prepared and evaluated for their capability of protection from blue light LEDinduced corneal damage as compared to CTC protective eye gel (1.25-7%, w/v). The findings pointed towards excellent protection of CTC gel formulations as compared to CTC eye drop formulations. In addition, the prepared optimized CTC gel had thixotropic behavior as evident from percentage structural recovery which was 1.75 fold higher than marketed formulation (I-Comfort, HPMC 2%, w/v). The safety and non-toxicity of CTC protective eye drop and gel were confirmed by HET-CAM test. Further, a rat eye model was implemented that mimic blue light light-emitting diode induced corneal damage in day to day life to assess the protective effect of CTC protective eye drop and gel. RESULTS: The order of protectiveness of CTC formulations was found to be CTC protective eye gel (4%, w/v) (no corneal damage)>marketed eye gel (12.34% corneal damage)=CTC protective eye drop (0.75%, w/v) (17.48% corneal damage)> marketed eye drop (51% corneal damage). The mechanism behind the protective effect of CTC eye drop and gel was associated with good free radical scavenging activity and corneal adhesive property of CTC. It is established from the present work that, carboxymethyl Terminalia catappa has protective action against blue light light-emitting diode induced corneal damage.

MSCs helped reduce scarring in the cornea after fungal infection when combined with anti-fungal treatment.

BACKGROUND: Fungal Keratitis (FK) is an infective keratopathy with extremely high blindness rate. The damaging effect of this disease is not only the destruction of corneal tissue during fungal infection, but also the cornea scar formed during the healing period after infection control, which can also seriously affect a patient's vision. The purpose of the study was to observe the effect of umbilical cord mesenchymal stem cells (uMSCs) on corneal scar formation in FK. METHODS: The FK mouse model was made according to a previously reported method. Natamycin eye drops were used for antifungal treatment 24 h after modeling. There are four groups involved in the study, including control group, FK group, vehicleinj FK group and uMSCsinj FK group. Mice in uMSCsinj FK group received repeated subconjunctival injections of uMSCs for 3 times at the 1d, 4d and 7d after FK modeling. At 14d, 21d and 28d after trauma, clinical observation, histological examination, second harmonic generation and molecular assays were performed. RESULTS: The uMSCs topical administration reduced corneal scar formation area and corneal opacity, accompanying with decreased corneal thickness and inflammatory cell infiltration, following down-regulated fibrotic-related factors α-SMA, TGFß1, CTGF, and COLI and finally inhibited phosphorylation of TGFß1/Smad2 signaling pathway during FK corneal fibrosis. CONCLUSION: The results confirmed that uMSCs can improve corneal opacity during the scar formation stage of FK, and exert anti-inflammatory and anti-fibrotic effects.

Perioperative Corneal Abrasions After Nonocular Surgery: A Systematic Review.

PURPOSE: To perform a systematic review of the international literature evaluating the risk factors, preventative steps, and treatments for perioperative corneal injuries for nonocular surgery. METHODS: PubMed, Embase, and Evidence-Based Medicine Reviews databases were searched on April 13, 2018. Two hundred four articles were identified with 16 meeting the inclusion criteria. All studies were evaluated for quality and level of evidence. Two types of studies were included. The first were primary epidemiological studies that looked at the rates of perioperative corneal injuries after nonocular surgery and the second were trials that either studied preventative steps or treatments. RESULTS: A statistical analysis was completed to reveal trends in perioperative corneal abrasions. Rates ranged from 0.01% to 59% with a cumulative rate of 0.64% (95% confidence interval 0.36%-1.35%). Primary risk factors were identified as longer procedures, general anesthesia, and advanced age. The most commonly associated ocular injuries were found to include chemical injury, conjunctivitis, blurred vision, and conjunctival congestion. Treatment strategies for corneal abrasion in the literature recommended erythromycin ointment and ample ocular lubrication for the fastest recovery. Education interventions alone, as studied in 2 of the 16 articles, demonstrated a significant decrease in the rate of corneal abrasions. CONCLUSIONS: Standardized ocular protection, reporting, and education initiatives were found to maximally decrease rates of perioperative corneal abrasions after nonocular surgery. However, no gold standard currently exists for intraoperative ocular protection. More research needs to be conducted on specific prevention strategies and content of educational initiatives in hopes of standard development across facilities nationwide.

Molecular basis of Mitomycin C enhanced corneal sensory nerve repair after debridement wounding.

The ocular surface is covered by stratified squamous corneal epithelial cells that are in cell:cell contact with the axonal membranes of a dense collection of sensory nerve fibers that act as sentinels to detect chemical and mechanical injuries which could lead to blindness. The sheerness of the cornea makes it susceptible to superficial abrasions and recurrent erosions which demand continuous regrowth of the axons throughout life. We showed previously that topical application of the antibiotic and anticancer drug Mitomycin C (MMC) enhances reinnervation of the corneal nerves and reduces recurrent erosions in mice via an unknown mechanism. Here we show using RNA-seq and confocal imaging that wounding the corneal epithelium by debridement upregulates proteases and protease inhibitors within the epithelium and leads to stromal nerve disruption. MMC attenuates these effects after debridement injury by increasing serpine1 gene and protein expression preserving L1CAM on axon surfaces of reinnervating sensory nerves. These data demonstrate at the molecular level that gene expression changes in the corneal epithelium and stroma modulate sensory axon integrity. By preserving the ability of axons to adhere to corneal epithelial cells, MMC enhances sensory nerve recovery after mechanical debridement injury.

Eye Protection in Liver Transplantation Patients Under General Anesthesia.

BACKGROUND: Opsite (Smith & Nephew, Hull, UK) is widely used in wound care but its use in eye protection against corneal abrasion during major surgery is rarely reported. The purpose of the current study is to compare the effectiveness of using Opsite in eye protection with either wet gauze alone or with wet gauze following application of eye ointment in patients undergoing living donor liver transplantation (LDLT). METHODS: This is a prospective, double-blinded, randomized controlled trial. Forty-one patients undergoing liver transplantation were enrolled. One eye of each patient was protected with sterile gauze soaked with normal saline solution and covered with Opsite. Duratears (ALCON, Fort Worth, Tex, United States) ointment was applied to the other eye before covering it with sterile wet gauze and Opsite (ointment group). The corneal examination was carried out after fluorescein staining before and at the end of surgery by the same doctor. A Student t-test and a χ2 test were used for the statistical analyses. RESULTS: Forty-one patients with 82 eyes were observed in this study. No corneal epithelial defects were found in either the normal saline group or the ointment group. CONCLUSION: Opsite combined with wet gauze with or without additional eye ointment provided 100% protection against corneal abrasion in patients undergoing LDLT.

An Engineered Human Fibroblast Growth Factor-1 Derivative, TTHX1114, Ameliorates Short-term Corneal Nitrogen Mustard Injury in Rabbit Organ Cultures.

Purpose: Organ cultures of rabbit corneas have been used to ascertain the effectiveness of a human fibroblast growth factor (FGF)-1 derivative (TTHX1114), lacking cysteine residues, to protect against and/or repair epithelial lesions following exposure to nitrogen mustard (NM). Methods: Rabbit corneas were exposed to NM and cultured for up to 14 days, with or without drug (TTHX1114). At specified times, tissue was examined by histopathology and graded by a novel composite scale. Proliferation was measured by 5-ethynyl-2'-deoxyuridine (EdU) incorporation, and the expression of native FGF-1 and ADAM-17 after NM exposure was determined by immunofluorescence. Results: Rabbit corneas, exposed to a single dose of NM, showed a nearly complete loss of epithelial cells by day 6 but were significantly regenerated by day 14. When treated continuously with TTHX1114 following vesicant exposure, the losses remained at day 2 levels. The loss of keratocytes in the stroma was not affected by TTHX1114. EdU incorporation over the same time course showed a steady increase in tissue that had not been treated with TTHX1114, while corneas that were treated with the drug showed a higher percent incorporation initially, which then decreased, indicating the strong proliferative response to TTHX1114. ADAM-17 was not significantly altered by TTHX1114 treatment. Corneal epithelial FGF-1 disappeared after only 1 day following exposure to NM. Conclusions: TTHX1114 is protective against NM-induced damage of the corneal epithelium, possibly by supplying an NM-resistant source of trophic support and by stimulating regeneration of new epithelial cells. These responses underscore the potential value of TTHX1114 as an anti-vesicant therapeutic.

Does oral spirulina protect the cornea from formaldehyde exposure? Application to anatomy laboratories.

In this study, the protective effect of spirulina on corneal injury after formaldehyde (FA) exposure was assessed. Thirty adult male albino rats were divided into four groups. Group I: 12 rats were divided into two subgroups: I-a (negative control) and I-b (positive control). Group II (spirulina group): six rats received spirulina via an oral gavage feeding needle at a daily dose of 400 mg/kg b.w. Group III (FA exposure group): six rats were subjected to 10% FA inhalation for 2 h per day for 2 weeks (5 days per week). Group IV (FA exposure group treated with spirulina): six rats were exposed to 10% FA as in group III, with co-administration of spirulina as in group II. After 2 weeks, all the rats were sacrificed; the corneas were dissected and processed for paraffin sections. The sections were stained with hematoxylin and eosin (H&E), Masson's trichrome (MTC), or avidin-biotin peroxidase, and examined by light microscopy. The sections of rat cornea exposed to FA (Group III) showed disorganized and compressed epithelium with erosions. Subepithelial mononuclear cell infiltration and invasion of blood vessels were also evident. Stromal collagen fibers were disorganized and widely separated. All these changes were ameliorated by administration of spirulina (Group IV). Corneal thickness was nearly normal in Group IV, statistically significantly less than in Group III. It was concluded that spirulina protects against FA-induced corneal injury in rats. Clin. Anat. 31:830-837, 2018. © 2018 Wiley Periodicals, Inc.

Thin Rigid Contact Lens Used in Vitreous-Retinal Surgery for Corneal Protection: A Randomized Controlled Trial.

PURPOSE: To design a rigid contact lens (CL) to be used in combination with a wide-angle viewing system and analyze its protection for corneal epithelial during vitreous-retinal surgery. METHODS: A thin and lightweight rigid CL was designed and constructed. The impact of the CL on the visualized fundus range was evaluated using a concrete eye model. Patients with severe proliferative diabetic retinopathy (PDR) were randomized to either the CL group, corneal protective agent (CPA) group, or balanced salt solution (BSS) group. All patients underwent phacoemulsification and a standard 23-gauge three-port vitrectomy. Surgery time and corneal fluorescein staining score (FSS) postoperatively were mainly measured. RESULTS: In the eye model, a larger area of fundus was visualized with the use of our CL under 128 D or 60 D Resight lens. The mean surgery time was 51.36±8.06 min, 50.89±8.26 min, and 55.46±9.14 in CL, CPA, and BSS group, respectively (F=2.325, P=0.105). In eight eyes in the BSS group, corneal epithelial layer was peeled off because the dryness of the cornea could not maintain a clear fundus image. The FSS in BSS group was markedly higher than that of CL and BSS group 1 day (P<0.001), 3 days (P<0.001), and 7 days (P=0.002) postoperatively. There was no statistical significance of the FSS between CL and CPA group at each follow-up endpoint. CONCLUSIONS: The CL that we designed can slightly enlarge the visible fundus range and efficiently protect corneal epithelium during vitrectomy for patients with PDR.

Alleviating effects of artificial tear instillation on S-1-induced ocular toxicity in dogs.

S-1 is an anticancer agent that consists of tegafur, gimeracil, and oteracil potassium at a molar ratio of 1:0.4:1. S-1 is used to treat metastatic and resectable gastric cancer. However, the extensive use of S-1 in clinical practice results in watery eyes, a serious clinical problem, which worsens patients' quality of life. Although repeated instillation of artificial tears is recommended, therapy or prophylaxis against S-1-induced ocular toxicity has not been established. In the present study, we evaluated the alleviating effects of repeated artificial tear instillation on S-1-induced ocular toxicity in dogs. Ten beagle dogs (5 males and 5 females) were orally administered 3 mg/kg/day of S-1 for up to 21 days. Five drops of artificial tears were instilled to the left eye, eight times daily, within 6 hr after S-1 administration. The mean cornea staining score tended to be low in the left eye with repeated artificial tear instillation. In 4 out of 10 dogs, the corneal staining score of the left eye was more than 2-fold lower than that of the right eye. The incidence of dogs indicating normal tear drainage increased and stenosed tear drainage decreased by repeated artificial tear instillation. In conclusion, we demonstrated that artificial tear instillation can alleviate corneal surface damage induced by S-1 in dogs.

Corneal Dose Reduction Using a Bismuth-Coated Latex Shield over the Eyes During Brain SPECT/CT.

This study aimed to determine whether a bismuth-coated latex shield (B-shield) could protect the eyes during brain SPECT/CT. Methods: A shield containing the heavy metal bismuth (equivalent to a 0.15-mm-thick lead shield) was placed over a cylindric phantom and the eyes of a 3-dimensional brain phantom filled with 99mTc solution. Subsequently, phantoms with and without the B-shield were compared using SPECT/CT. The CT parameters were 30-200 mA and 130 kV. The dose reduction achieved by the B-shield was measured using a pencil-shaped ionization chamber. The protective effects of the B-shield were determined by evaluating relative radioactivity concentration as well as artifacts (changes in CT number), linear attenuation coefficients, and coefficients of variation on SPECT images. Results: The radiation doses with and without the B-shield were 0.14-0.77 and 0.36-1.93 mGy, respectively, and the B-shield decreased the average radiation dose by about 60%. The B-shield also increased the mean CT number, but only at locations just beneath the surface of the phantom. Streaks of higher density near the underside of the B-shield indicated beam hardening. Linear attenuation coefficients and the coefficients of variation did not significantly differ between phantoms with and without the B-shield, and the relative 99mTc radioactivity concentrations were not affected. Conclusion: The B-shield decreased the radiation dose without affecting estimated attenuation correction or radioactivity concentrations. Although surface artifacts increased with the B-shield, the quality of the SPECT images was acceptable. B-shields can help protect pediatric patients and patients with eye diseases who undergo SPECT imaging.

Grooved Glaucoma Drainage Devices That Continuously Deliver Cyclosporine A Decrease Postsurgical Scar Formation in Rabbit Eyes.

Purpose: To study the functional outcomes of filtration surgery by implanting improved glaucoma drainage devices (GDDs) comprising surface grooves and a composite coating of cyclosporine A (CsA) and PLGA in experimental rabbit eyes. Methods: Improved GDDs were designed and prepared by modifying normal GDD with surface grooves and a CsA-PLGA composite coating. Normal GDDs, grooved GDDs (G-GDDs), and G-GDDs with a CsA-PLGA composite coating (CsA@G-GDD) were implanted into 18 rabbit eyes (six eyes per group). The intraocular pressure (IOP), bleb survival time, bleb morphology, and anterior chamber reactions were assessed for up to 12 weeks after GDD implantation. The IOPs were compared statistically among the three groups. Bleb morphology was quantified using the Indiana Bleb Appearance Grading Scale. Anterior chamber radiography was performed to check whether the filtrating pathway was blocked, and determine the drainage time and diffusion area of the contrast agent. Hematoxylin and eosin staining and immunohistochemistry were conducted to assess how the GDDs slowed or prevented scar formation. Results: The improved GDDs were successfully prepared and implanted in 18 rabbit eyes without severe surgical complications. Bleb survival time was significantly longer and IOP was significantly lower in the G-GDD and CsA@G-GDD groups compared with the GDD group (all, P < 0.001). Blebs were significantly higher in the CsA@G-GDD group than in the GDD and G-GDD groups (P = 0.003). Anterior chamber radiography revealed more unobstructed filtration channels in the CsA@G-GDD group than in the GDD group (P = 0.032). Postsurgical scar formation was less extensive in the G-GDD and CsA@G-GDD groups than in the GDD group. Conclusions: Compared with the normal GDDs, G-GDDs with a CsA-PLGA coating inhibited postsurgical scar formation and improved the surgical success rate, and might represent an alternative to existing glaucoma filtration devices.

Selenium-binding lactoferrin is taken into corneal epithelial cells by a receptor and prevents corneal damage in dry eye model animals.

The ocular surface is strongly affected by oxidative stress, which causes many ocular diseases including dry eye. Previously, we showed that selenium compounds, e.g., selenoprotein P and Se-lactoferrin, were candidates for treatment of dry eye. This paper shows the efficacy of Se-lactoferrin for the treatment of dry eye compared with Diquas as a control drug using two dry eye models and incorporation of lactoferrin into corneal epithelial cells via lactoferrin receptors. We show the efficacy of Se-lactoferrin eye drops in the tobacco smoke exposure rat dry eye model and short-term rabbit dry eye model, although Diquas eye drops were only effective in the short-term rabbit dry eye model. These results indicate that Se-lactoferrin was useful in the oxidative stress-causing dry eye model. Se-lactoferrin was taken into corneal epithelium cells via lactoferrin receptors. We identified LRP1 as the lactoferrin receptor in the corneal epithelium involved in lactoferrin uptake. Se-lactoferrin eye drops did not irritate the ocular surface of rabbits. Se-lactoferrin was an excellent candidate for treatment of dry eye, reducing oxidative stress by a novel mechanism.

Corneal Injury from Presurgical Chlorhexidine Skin Preparation.

BACKGROUND: Chlorhexidine skin preparation has been shown to provide highly effective antimicrobial presurgical skin cleansing. However, there is a significant risk of ocular toxicity when it is used in periocular areas. CASE DESCRIPTION: We describe 2 cases of significant corneal damage resulting from 4% chlorhexidine gluconate preoperative skin cleanser, despite the use of protective occlusive dressing over the eyes. Because of the potential for severe corneal toxicity resulting from use of chlorhexidine, alternative agents such as 10% povidone-iodine should be considered for skin preparation near periocular areas whenever possible. CONCLUSIONS: If chlorhexidine gluconate must be employed near periocular areas, great care must be exercised to avoid contact with the eyes, and additional protective measures (e.g., absorbent eye pads along with tightly occlusive dressings) must be used whenever possible.