Celastrol alleviates subconjunctival fibrosis induced by silicone implants mimicking glaucoma surgery.

Subconjunctival fibrosis is critical to the outcomes of several ophthalmic conditions or procedures, such as glaucoma filtering surgery. This study aimed to investigate the anti-fibrotic effect of celastrol on subconjunctival fibrosis and to further reveal the underlying mechanisms. We used celastrol-loaded nanomicelles hydrogel hybrid as a sustained-release drug. A rabbit model of subconjunctival fibrosis following silicone implantation was used for in vivo study, and TGF-ß1-induced human pterygium fibroblast (HPF) activation as an in vitro model. The effects of celastrol on inhibiting TGF-ß1-induced migration and proliferation of HPFs were evaluated by scratch wound assay and CCK-8, respectively. Immunofluorescence and western blotting were used to examine the effect of celastrol on the expression of α-SMA, collagen I, fibronectin, and the targets of the Hippo signaling pathway. We found that in vivo celastrol treatment reduced the expression of YAP and TAZ in subconjunctival tissue. Moreover, celastrol alleviated collagen deposition and subconjunctival fibrosis at 8 weeks. No obvious tissue toxicity was observed in the rabbit models. Mechanistically, celastrol significantly inhibited TGF-ß1-induced proliferation and migration of HPFs. Pretreatment of HPFs with celastrol also suppressed the TGF-ß1-induced protein expression of α-SMA, collagen I, fibronectin, TGF-ßRII, phosphorylated Smad2/3, YAP, TAZ, and TEAD1. In conclusion, celastrol effectively prevented subconjunctival fibrosis through inhibiting TGF-ß1/Smad2/3-YAP/TAZ pathway. Celastrol could serve as a promising therapy for subconjunctival fibrosis.

Can bleeding in trabeculectomy be decreased? Effectiveness of brimonidine pre-treatment.

PURPOSE: To evaluate the efficacy of preoperative topical brimonidine use to maintain visibility during trabeculectomy and control intraoperative bleeding and postoperative subconjunctival hemorrhage. METHODS: The first group comprised 35 eyes of 34 patients administered brimonidine tartrate 0.15% (Brimogut, Bilim Ilac, Turkey) eye drops 6 and 3 min before surgery, and 33 eyes of 31 patients who received no medication for vasoconstriction formed the second group. Preoperative and postoperative photographs and operation video images were taken and vision analysis software used. Black-and-white images were obtained to identify the blood vessel and surface hemorrhage areas. The surface area of the hemorrhage was calculated by counting the black pixels with Image J software. RESULTS: There was no significant difference between two groups in terms of baseline (preoperative) eye redness (p > 0.05). In the first group, the eye redness values were 344.7 ± 19.5 pixels preoperatively and 244.1 ± 23.3 pixels at the beginning of the surgery, respectively (p < 0.001). However, no significant change was observed in the second group in eye redness (348.2 ± 17.5 pixels preoperatively and 360.7 ± 26.8 pixels at the beginning of the surgery, p > 0.05). Cautery was used for an average of 11.91 ± 1.96 s in the first group and 25.57 ± 4.66 s in the second to control intraoperative bleeding (P < 0.001). CONCLUSION: Preoperative topical brimonidine use in trabeculectomy surgery significantly decreased intraoperative bleeding and postoperative subconjunctival hemorrhage and facilitated bleeding control.

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.

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

PURPOSE: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. METHODS: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. RESULTS: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. CONCLUSION: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.

Oxymetazoline: reduction of subconjunctival hemorrhage incidence after intravitreal injections.

OBJECTIVE: Subconjunctival hemorrhage (SCH) is an important minor side effect that might affect patient compliance to antivascular endothelial growth factor (anti-VEGF) intravitreal injection treatment (IVI). We sought to compare SCH incidence and pain score responses after topical oxymetazoline in naïve patients undergoing a single IVI of ranibizumab for diabetic macular edema. METHODS: Prospective, randomized, double-blinded, single centre study. One hundred two patients naïve to anti-VEGF were assigned to receive either topical oxymetazoline or placebo 30 minutes before IVI. SCH incidence and area were measured by slit lamp 24 hours after, and pain was evaluated 5 minutes and 24 hours after. RESULTS: SCH incidence was reported on 72% in control group versus 51% in oxymetazoline group (p = 0.037). Mean size of SCH was 16.82 mm2 in control group versus 12.55 mm2 in oxymetazoline group (p = 0.394). Prevalence of local pain in the overall study population was 60%. No significant statistical difference was achieved between groups 5 minutes or 24 hours after IVI in either pain scale evaluation. CONCLUSION: Administration of topical oxymetazoline 30 minutes before IVI is a single, harmless, cost-effective intervention that decreases the incidence of subconjunctival hemorrhage. This may considerably improve patient treatment satisfaction and promote compliance to IVI therapy.

Bleb Needling with Mitomycin C as Adjunctive Therapy in Failing Blebs: A Retrospective Study.

PURPOSE: To evaluate the effects and complications related to use of mitomycin C (MMC) as an adjunctive therapy in bleb needling. METHODS: Retrospective review of the records of patients affected by open-angle glaucoma who underwent a bleb revision as a treatment for failed trabeculectomy. All subjects underwent surgery with a fornix-based approach to incision. Full baseline data for each patient included a comprehensive ocular and medical history, the patient's Snellen visual acuity test results, and Goldmann applanation tonometry test results. Data were reported following observations occurring at 6, 12, 18, 24, and 30 months. In addition, the number and timing of needling with or without MMC subconjunctival injections and any short- and long-term complications were observed. RESULTS: We included 101 patients, 56 (55.4%) male and 45 (44.6%) female. The mean age was 69.81 ± 16.19 years (range 28-92). Statistically significant effects of needling and needling and MMC (p values <0.05) in the decrease in intraocular pressure were observed. Three (2.9%) patients presented hypotony at the last follow-up visit. No other complications were observed. CONCLUSIONS: Needling bleb revision augmented with the use of MMC appears to be a more useful tool in the management of failing bleb.

Daily versus monthly disposable contact lens: Which is better for ocular surface physiology and comfort?

PURPOSE: To investigate the effect of soft contact lenses (SCL) wearing modality and lens materials on the changes in conjunctival bulbar and limbal redness and conjunctival and corneal staining after two months of SCL wear. Comfort level was also analyzed. METHODS: In this longitudinal clinical trial, forty-seven neophyte myopic subjects were fitted with a monthly disposable lens (lotrafilcon-B or comfilcon-A or balafilcon-A) in one eye and a daily disposable lens (nelfilcon-A or stenofilcon-A or nesofilcon-A) in the other eye, randomly selected. Conjunctival bulbar and limbal redness and conjunctival and corneal staining were evaluated before and after lens wear. Effect of lens wearing modality and lens materials on these changes was also determined. Level of comfort was evaluated subjectively twice per day. Comfort level and reduction in end-of-day comfort were compared between different lens wearing modalities and materials. RESULTS: Bulbar and limbal redness and conjunctival and corneal staining were increased (p<0.001) after lens wear, and changes were similar with daily and monthly disposable lens wear (p>0.05). Limbal redness was associated with lens materials, and lotrafilcon-B induced the least among the studied lenses (p<0.05). There was no significant association between the wearing modality and the average comfort level and reduction of end-of-day comfort (p>0.05). CONCLUSION: Two months of SCL wear increased conjunctival redness, conjunctival and corneal staining, which were not associated with the lens wearing modality. There was a reduction in end-of-day comfort, similar to daily and monthly lenses. The change in limbal redness and reduction in end-of-day comfort were associated with the characteristics of the lens material.

Can We Improve the Tolerance of an Ocular Prosthesis by Enhancing Its Surface Finish?

PURPOSE: Patients who wear an ocular prosthesis frequently suffer with dry eye symptoms and socket discharge, often on a daily basis. The aim of the study was to determine whether a smoother, optical quality polish of the prosthesis' surface could improve symptoms and wear tolerance. The study was designed as single-center, single-masked, prospective randomized controlled trial. Eighty-eight consecutive patients undergoing annual ocular prosthesis maintenance review were approached from the prosthesis clinic. Forty-one out of 49 eligible patients were recruited. METHODS: Participants were randomized to either a standard or a higher "optical quality" polish of their prosthesis. At entry to the trial, at 1 month, and 12 months they completed a questionnaire covering cleaning, lubricant use, inflammation, discomfort, and discharge. Lower scores indicated better tolerance of the prosthesis. At each visit, the prosthesis was stained and photographed against a standard background to assess deposit build up. Primary outcome measures were 1) a subjective questionnaire score and 2) an objective assessment of surface deposit build-up on prosthetic eyes by standardized photographic grading. RESULTS: Forty-one patients participated in the study. The median age of their prosthesis was 36 months (range 9 months-40 years). There was no statistically significant difference in questionnaire scores or deposit build up between the 2 groups at baseline. By 12-months, the higher optical quality polish showed a statistically significant reduction in symptoms and frequency of discharge (2.19 vs. 3.85; p = 0.05-lower scores better). Scoring of the prosthesis' deposit build-up showed a significant difference at 1 month, but this was not sustained at 12 months. CONCLUSIONS: Creating an optical quality finish to an ocular prosthesis reduces deposit build up on artificial eyes. The authors found this modification improved patient tolerance at 12 months.

Unique Venous Drainage of a Sphenoid Wing Dural Arteriovenous Fistula with Ocular Symptoms.

BACKGROUND: Dural arteriovenous fistulas (DAVFs) presenting with ocular symptoms, such as exophthalmos and chemosis, are commonly situated in the cavernous sinus (CS). DAVFs at the sphenoid wing with a drainage route into the superior orbital vein (SOV) should be considered as one of the differential diagnoses of ocular symptoms. CASE DESCRIPTION: A 41-year-old woman presented with progressive left-sided chemosis and proptosis after left pulsating tinnitus that disappeared spontaneously. Cerebral angiography showed that the fistula was situated along the inferior edge of the superior orbital fissure on the greater sphenoid wing and drained solely into the SOV without flowing into the CS that caused ocular symptoms. Transvenous selective catheterization was performed via the facial vein and SOV. The fistula was then embolized using detachable coils. CONCLUSIONS: After embolization, the ocular symptoms resolved, and the patient was discharged without neurologic deficit. Herein, we discuss the developmental mechanism of the unique drainage pattern, including the clinical symptoms and anatomic features of greater sphenoid wing DAVFs.

[Ocular Surface Evaluation in Patients Treated with Prostaglandin Analogues Considering Preservative Agent]. / Hodnocení ocního povrchu u pacientu lécených analogy prostaglandinu s ohledem na obsazenou konzervacní látku.

PURPOSE: The aim of this study was to evaluate the ocular surface in patients treated with prostaglandin analogues considering contained preservative agent. METHODS: 60 patients with glaucoma or ocular hypertension treated with prostaglandin analogue monotherapy were enrolled in this observational study. 20 patients with glaucoma suspect or ocular hypertension without local or systemic glaucoma medication formed the control group. Demographic data and medical history were recorded for each participant. Patients filled in the Ocular surface disease index© (OSDI) questionnaire and underwent an ophthalmological examination including assessment of conjunctival hyperaemia according to Efron, tear film break up time (BUT) and fluorescein staining according to the Oxford grading scheme. Treated participants were divided into 3 groups according to the preservative contained in the currently used prostaglandin analogue: the preservative-free group (18 patients), the polyquaternium group (17 patients) and the benzalkonium chloride (BAK) group (25 patients). RESULTS: The control group had significantly lower fluorescein staining than the preservative-free group (p=0.001), the polyquaternium group (p=0.007) and the BAK group (p=0.002). The conjunctival hyperaemia was significantly lower in the preservative-free group compared to the polyquaternium group (p=0.011). There was no significant difference among the other groups. The difference neither in the OSDI score nor in the BUT was statistically important. CONCLUSION: This study confirmed that the ocular surface is worse in patients treated with prostaglandin analogue monotherapy than in people without glaucoma medication. A significant difference among treated patients depending on a preservative agent was not proved.Key words: benzalkonium chloride, glaucoma, ocular surface disease, preservatives, prostaglandin analogues.

Long-term Safety and Efficacy of Latanoprostene Bunod 0.024% in Japanese Subjects with Open-Angle Glaucoma or Ocular Hypertension: The JUPITER Study.

INTRODUCTION: Latanoprostene bunod (LBN) is a novel nitric oxide (NO)-donating prostaglandin F2α analog. We evaluated the long-term safety and intraocular pressure (IOP)-lowering efficacy of LBN ophthalmic solution 0.024% over 1 year in Japanese subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: This was a single-arm, multicenter, open-label, clinical study. Subjects aged 20 years and older with a diagnosis of OAG or OHT instilled 1 drop of LBN ophthalmic solution 0.024% in the affected eye(s) once daily in the evening for 52 weeks and were evaluated every 4 weeks. Safety assessments included vital signs, comprehensive ophthalmic exams, and treatment-emergent adverse events (AEs). Absolute and percent reductions from baseline in IOP were also determined. RESULTS: Of 130 subjects enrolled, 121 (93.1%) completed the study. Mean age was 62.5 years, and mean (standard deviation) baseline IOP was 19.6 (2.9) and 18.7 (2.6) mmHg in study eyes and treated fellow eyes, respectively. Overall, 76/130 (58.5%) and 78/126 (61.9%) subjects experienced ≥1 AEs in study eyes and treated fellow eyes, respectively. In both study eyes and treated fellow eyes, the most common AEs were conjunctival hyperemia, growth of eyelashes, eye irritation, and eye pain. At 52 weeks, 9% of treated eyes had an increase in iris pigmentation compared with baseline based on iris photographs. No safety concerns emerged based on vital signs or other ocular assessments. Mean reductions from baseline in IOP of 22.0% and 19.5% were achieved by week 4 in study and treated fellow eyes, respectively. These reductions were maintained through week 52 (P < 0.001 vs. baseline at all visits). CONCLUSION: Once daily LBN ophthalmic solution 0.024% was safe and well-tolerated in Japanese subjects with OAG or OHT when used for up to 1 year. Long-term treatment with LBN ophthalmic solution 0.024% provided significant and sustained IOP reduction. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01895972. FUNDING: Bausch & Lomb, Inc. a division of Valeant Pharmaceuticals International Inc.

Effects of Gelatin Hydrogel Loading Mitomycin C on Conjunctival Scarring in a Canine Filtration Surgery Model.

PURPOSE: To investigate the effects and toxicities of gelatin hydrogel (GH) loading mitomycin C (MMC) on IOP and conjunctival scarring in a canine model of glaucoma surgery in comparison with conventional MMC application. METHODS: Glaucoma surgery models were made in six beagles. An MMC-loaded GH was implanted under the conjunctiva of one eye (GH-MMC group) and 0.04% MMC-soaked sponges were placed under the conjunctiva of the other eye (MMC group) for 5 minutes. Intraocular pressures and bleb features were then assessed for 4 weeks postoperative, followed by histological evaluation. The ratio of conjunctival area to scleral area, the densities of collagen and the numbers of fibroblasts, vessels, and proliferative cell nuclear antigen (PCNA)-positive cells were then quantified. RESULTS: In both groups, IOP reduction and bleb formation were maintained in a similar manner for 4 weeks postoperative. No significant difference in the ratio of conjunctival area to scleral area was found between the two groups. Collagen density and the numbers of fibroblasts and vessels were significantly lower in the MMC-treated group than in the GH-MMC-treated group. No significant difference in PCNA-positive cells was found between the two groups. CONCLUSIONS: Implantation of MMC-loaded GH ameliorated toxicity to conjunctiva compared with the 5-minute placement of MMC, whereas its effect on IOP reduction and bleb formation was similar. These results suggest that using GH for the application of MMC is a safer method than the conventional application of MMC in glaucoma filtration surgery.

The effect of a temperature-sensitive poloxamer-alginate-CaCl2 mixture after strabismus surgery in a rabbit model.

PURPOSE: To determine the efficacy of a temperature-sensitive poloxamer-alginate mixture in reducing adhesions after strabismus surgery in a rabbit model. METHODS: The superior rectus muscle was recessed in each of 36 eyes from 18 rabbits. One randomly assigned eye in each rabbit was treated with a poloxamer-alginate mixture (PA group); the other eye was treated with a subconjunctival injection of saline (control group). The adhesions between the superior rectus muscle, sclera, and conjunctiva were clinically evaluated by a masked observer at 1 day, 1 week, and 4 weeks after surgery. Inflammation was analyzed by hematoxylin and eosin staining and anti-CD11b staining. Late fibrosis was assessed by the Masson trichrome and α-smooth muscle actin staining. Adhesion, inflammation, and fibrosis were graded on a scale of 0-4. RESULTS: There was no significant between-group difference in the degree of adhesion at 1 day and 4 weeks after surgery. However, the degree of adhesion in the PA group was lower than that in the control group at postoperative week 1 (P < 0.05). Acute inflammation was similar between the groups (P > 0.05). At postoperative week 4, inflammatory cell infiltration was reduced in the PA group (P = 0.046). A significant between-group difference in late fibrosis at postoperative week 4 was observed through the Masson trichrome (P = 0.024) and α-smooth muscle actin staining (P = 0.025). CONCLUSIONS: The poloxamer-alginate mixture significantly decreased adhesion after strabismus surgery in a rabbit model. Additional studies are warranted to evaluate the use of this mixture in preventing postoperative adhesions.

Dietary α-lipoic acid prevents UVB-induced corneal and conjunctival degeneration through multiple effects.

PURPOSE: This study investigated the effects of dietary α-lipoic acid (α-LA) against ultraviolet B (UVB)-induced corneal and conjunctival degeneration in a mouse model. METHODS: Female CBA mice were randomly divided into five study groups, including blank control, UVB without α-LA, and UVB with dietary α-LA at 1, 10, and 100 mg/kg body weight. Following UVB exposure, corneal surfaces were assessed along with immunohistochemistry for nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), malondialdehyde (MDA) accumulation, and P63⁺ basal cell distribution. Matrix metalloproteinase (MMP)-2 and MMP-9 activities were determined by gelatin zymography. ELISA assay was performed to confirm the findings of immunohistochemistry for NF-κB, COX-2, and MDA, along with the levels of TNF-α and IL-6. Tear production and goblet cell density were determined after tear strip assay and periodic acid Schiff staining, respectively. RESULTS: The results showed that UVB irradiation caused corneal surface damage, polymorphonuclear leukocyte infiltration, and loss of P63⁺ basal cells. Dietary α-LA ameliorated the UVB-induced corneal damage while simultaneously reducing MDA accumulation and maintaining P63⁺ basal cell survival. NF-κB-p65, COX-2, TNF-α, IL-6, and MMP-9 activity were all reduced by dietary α-LA. In addition, α-LA helped to reverse aqueous tear reduction, conjunctival squamous epithelium metaplasia, and goblet cell loss after UVB exposure. CONCLUSIONS: Dietary α-LA can prevent UVB-induced corneal damage and can be used as a prophylactic agent prior to excessive UVB exposure.

Influence of incisional vitreous incarceration in sclerotomy closure competency after transconjunctival sutureless vitrectomy.

PURPOSE: To evaluate the influence that vitreous incarceration may exert on the presence of postoperative conjunctival blebs over sclerotomies after transconjunctival sutureless vitrectomy (TSV). Blebs are formed by incisional leakage due to incompetent closure. METHODS: Experimental study in which 23-gauge TSV was performed in 146 cadaveric pig eyes. Once the vitrectomy was finished, triamcinolone was injected inside the vitreous cavity for staining residual vitreous, one of the superior cannulas was extracted over the light probe, and the other cannula was removed with the plug inserted. Postoperative conjunctival blebs in superior sclerotomies were assessed by anterior-segment optical coherence tomography (AS-OCT) in a masked fashion; nondetectable blebs were classified as grade 0 (B0), thin bleb (≤half scleral thickness) as grade 1 (B1), and thick bleb (>half scleral thickness) as grade 2 (B2). Postoperative incisional vitreous entrapment was evaluated by slit-lamp photographs in a masked way; no incarceration was classified as grade 0 (V0), thin incarceration as grade 1 (V1), and thick incarceration as grade 2 (V2). RESULTS: Conjunctival blebs were found in 13.7% of the sclerotomies (11.3% bleb-B1, 2.4% bleb-B2). Vitreous incarceration was found in 96.5% of the sclerotomies without bleb (B0), 81.8% of the incisions with bleb-B1, and 14.3% of the wounds with bleb-B2. Vitreous incarceration was significantly associated with the absence of conjunctival bleb (P < 0.001). CONCLUSIONS: Vitreous incarceration in sclerotomies is related to less incisional leakage in our experimental model. Maneuvers that reduce vitreous entrapment, such as the interposition of a nonhollow probe during the cannula extraction, could decrease the sclerotomy closure competency.

Glaucoma therapy and ocular surface disease: current literature and recommendations.

PURPOSE OF REVIEW: To provide an update on clinical and experimental literature for ocular surface effects of glaucoma therapy and to provide practical guidelines for ophthalmologists treating glaucoma patients with ocular surface disease (OSD). RECENT FINDINGS: Preservatives, notably benzalkonium chloride (BAK), continue to contribute to OSD and demonstrate a variety of toxic ocular effects both in-vitro, and in animal/human studies. Recent literature frequently compares BAK with Polyquad, SofZia, and preservative-free therapies. Some clinical benefit has been demonstrated with newer BAK-free alternatives. SUMMARY: BAK-free and preservative-free therapies are becoming available but are not always a feasible alternative. It is important to recognize different clinical manifestations of allergy and chronic inflammation and to discuss options for patients experiencing OSD.

Suppression of avascular bleb formation by a thin biodegradable film in a rabbit filtration surgery with mitomycin C.

BACKGROUND: Avascularity of the bleb is regarded as a risk of bleb infection, which is the most serious complication after filtration surgery with mitomycin C (MMC). There is no perfect way to prevent avascular bleb formation. We hypothesized that keeping the conjunctiva away from direct exposure to aqueous filtration may suppress avascular bleb formation after filtration surgery with MMC. In order to prove our hypothesis, we investigated whether a thin biodegradable, honeycomb-patterned film (HPF) can reduce bleb avascularity in a rabbit model of filtration surgery with mitomycin C (MMC). METHODS: A fornix-based full-thickness filtration surgery was performed in one eye of each of five rabbits (control group). The same surgery with intraoperative MMC treatment was done in both eyes of six rabbits, with one eye receiving a 14-µm-thick HPF made from poly(L-lactide-co-ε-caprolactone), which was placed subconjunctivally over the filtration site with the honeycomb surface facing up. Intraocular pressure (IOP) measurements, bleb evaluations using ultrasound biomicroscopy (UBM), and in vivo confocal microscopy (IVCM) were performed periodically for 4 weeks postoperatively followed by histological examination. RESULTS: The postoperative IOP decrease and bleb survival were significantly greater in MMC-treated eyes than in control eyes, and were similar between MMC-only and MMC + HPF eyes. The avascular area in the bleb persisted for 4 weeks in MMC-only eyes. Postoperative IVCM showed morphological changes of the conjunctival epithelial cells (i.e., enlarged and variable in size and shape) and epithelial defects in MMC-only eyes, and significantly lower density of connective tissue and vascularity in the subepithelial space in MMC-only eyes compared to the control eyes. These IVCM findings agreed with those by UBM and histology. Bleb avascularity shown by clinical bleb appearance, IVCM and histology, conjunctival epithelial damage shown by IVCM and histology, and loose subepithelial connective tissue shown by UBM, IVCM, and histology were all reduced in MMC + HPF eyes compared to MMC-only eyes. CONCLUSIONS: IVCM successfully showed the characteristic conjunctival damage in MMC-treated blebs. The concomitant use of a thin biodegradable HPF reduced avascularity and conjunctival damage in blebs, without compromising filtration in rabbits following filtration surgery with MMC.

The effect of additional topical cyclosporine or vitamin A on the ocular surface during antiglaucoma medication administration.

PURPOSE: To investigate the effects of topical application of cyclosporine or vitamin A on the ocular surface during the concurrent administration of antiglaucoma drugs. METHODS: Thirty rabbits were randomized into 5 groups. Group 1 was administered timolol, group 2 received travoprost, group 3 received a travoprost/timolol fixed combination solution, group 4 received timolol and travoprost, and group 5 received timolol, travoprost, and dorzolamide. Each group was divided into a subgroup that received only the antiglaucoma medication (subgroup A), a subgroup that received topical cyclosporine in addition to the antiglaucoma medication (subgroup B), and a subgroup that received topical vitamin A in addition to the antiglaucoma medication (subgroup C). Conjunctival impression cytology specimens were collected at baseline and at weeks 1, 3, and 6. Conjunctival biopsy specimens were collected at week 6. RESULTS: The impression cytologic study results are as follows: statistically significant differences were found between groups 4A and 4B and between groups 4A and 4C at week 6 (p = 0.004, p = 0.006, respectively) and between groups 5A and 5B and between groups 5A and 5C at weeks 3 and 6 (p = 0.006, p = 0.008 at week 3, p = 0.003, p = 0.004 at week 6, respectively). No statistically significant differences were found between subgroup B and subgroup C in any of the groups at any of the times evaluated (p > 0.05). The conjunctival biopsy specimens from groups 1, 2, and 3 showed no distortion, but groups 4A and 5A showed distortion of the conjunctival epithelial structures. Groups 4B, 4C, 5B, and 5C showed less distortion of the conjunctival epithelial structures. CONCLUSION: Administration of cyclosporine or vitamin A may reduce the adverse ocular surface changes caused by long-term administration of antiglaucoma drugs.

Modulation of postoperative scarring with tacrolimus and octreotide in experimental glaucoma filtration surgery.

PURPOSE: The purposes of this study were to investigate the effects of topically administrated Tacrolimus and Octreotide on modulation of postoperative scarring in experimental glaucoma filtration surgery and to compare the antifibrotic properties of these agents with mitomycin-C (MMC). MATERIAL AND METHODS: A total of 28 New Zealand rabbits weighing 2.5-3 kg were randomly divided into a surgical control (SC) group and three experimental groups. Standard filtration surgeries were performed on the right eyes of all the rabbits. The rabbits in the SC group received only vehicle after the surgeries, whereas the rabbits in the three experimental groups were treated either with 0.4 mg/mL MMC during the surgery (MMC group) or with 0.3 mg/mL Tacrolimus drop four times a day (TT group) or with 10 µg/mL Octreotide drop three times a day (OT group) for 14 days. The animals were killed on day 14, eyes were enucleated and histologically and immunohistochemically analyzed. RESULTS: In SC group mean fibroblast, mononuclear cell number and fibroblast growth factor-ß (FGF-ß), transforming growth factor-ß (TGF-ß) immunostaining intensity was higher than all treatment groups. In OT group mean fibroblast number was lesser than MMC (p < 0.01) and TT (p < 0.05) group. In TT group mean fibroblast number was lesser than MMC group (p < 0.05). Mean mononuclear cell number was similar between MMC, OT and TT groups (p > 0.05). In MMC, OT and TT groups mean TGF-ß and FGF-ß immunostaining intensity was similar (p > 0.05). CONCLUSIONS: Topically administration of Tacrolimus and Octreotide effectively reduced the subconjuntival scarring response 2 weeks after experimental glaucoma filtration surgery.