Sirolimus loaded chitosan functionalized poly (lactic-co-glycolic acid) (PLGA) nanoparticles for potential treatment of age-related macular degeneration.

The usefulness of sirolimus (SIR) in the treatment of diseases that involve retinal degeneration like age-related macular degeneration (AMD) has been well documented. However, the problem still remains probably owing to the peculiar environment of the eye and/or unfavourable physiochemical profile of SIR. In the present work, we aimed to fabricate sirolimus loaded PLGA nanoparticles (SIR-PLGA-NP) and chitosan decorated PLGA nanoparticles (SIR-CH-PLGA-NP) to be administered via non-invasive subconjunctival route. Both the nanoparticles were characterized in terms of size, zeta potential, DSC, FTIR and XRD analysis. Quality by Design (QbD) approach was employed during the preparation of nanoparticles and the presence of chitosan coating was confirmed through thermogravimetric analysis and contact angle studies. Cationic polymer modification showed sustained in-vitro SIR release and enhanced ex-vivo scleral permeation and penetration. Further, SIR-CH-PLGA-NP revealed enhanced cellular uptake and thus, reduced lipopolysaccharide (LPS)-induced free-radicals generation by RAW 264.7 cells. The prepared nanoparticles were devoid of residual solvent and were found to be safe in HET-CAM analysis, RBCs damage analysis and histopathology studies. Moreover, high anti-angiogenic potential was observed in SIR-CH-PLGA-NP compared with SIR-PLGA-NP in chorioallantoic membrane (CAM) test. Overall, the current work opens up an avenue for further investigation of CH-PLGA-NP as SIR nanocarrier in the treatment of AMD.

VIP Stabilizes the Cytoskeleton of Schlemm's Canal Endothelia via Reducing Caspase-3 Mediated ZO-1 Endolysosomal Degradation.

OBJECTIVES: In glaucomatous eyes, the main aqueous humor (AH) outflow pathway is damaged by accumulated oxidative stress arising from the microenvironment, vascular dysregulation, and aging, which results in increased outflow resistance and ocular hypertension. Schlemm's canal (SC) serves as the final filtration barrier of the main AH outflow pathway. The present study is aimed at investigating the possible regulation of vasoactive intestinal peptide (VIP) on the cytoskeleton by stabilizing ZO-1 in SC. METHODS: Model of chronic ocular hypertension (COH) induced by episcleral venous cauterization was treated with topical VIP. The ultrastructure of junctions, ZO-1 levels, and permeability of the SC inner wall to FITC-dextran (70 kDa) were detected in the COH models. The F-actin distribution, F/G-actin ratio, and ZO-1 degradation pathway in human umbilical vein endothelial cells (HUVECs) and HEK 293 cells were investigated. RESULTS: ZO-1 in the outer wall of the SC was less than that in the inner wall. COH elicited junction disruption, ZO-1 reduction, and increased permeability of the SC inner wall to FITC-dextran in rats. ZO-1 plays an essential role in maintaining the F/G-actin ratio and F-actin distribution. VIP treatment attenuated the downregulation of ZO-1 associated with COH or H2O2-induced oxidative damage. In H2O2-stimulated HUVECs, the caspase-3 inhibitor prevents ZO-1 disruption. Caspase-3 activation promoted endolysosomal degradation of ZO-1. Furthermore, a decrease in caspase-3 activation and cytoskeleton redistribution was demonstrated in VIP + H2O2-treated cells. The knockdown of ZO-1 or the overexpression of caspase-3 blocked the effect of VIP on the cytoskeleton. CONCLUSION: This study provides insights into the role of VIP in stabilizing the interaction between the actin cytoskeleton and cell junctions and may provide a promising targeted strategy for glaucoma treatment.

History, presence, and future of mitomycin C in glaucoma filtration surgery.

PURPOSE OF REVIEW: Mitomycin C (MMC) is an alkylating agent with extraordinary ability to crosslink DNA, preventing DNA synthesis. By this virtue, MMC is an important antitumor drug. In addition, MMC has become the gold standard medication for glaucoma filtration surgery (GFS). This eye surgery creates a passage for drainage of aqueous humor (AqH) out of the eye into the sub-Tenon's space with the aim of lowering the intraocular pressure. A major cause of failure of this operation is fibrosis and scarring in the sub-Tenon's space, which will restrict AqH outflow. Intraoperative application of MMC during GFS has increased GFS success rate, presumably mainly by reducing fibrosis after GFS. However, still 10% of glaucoma surgeries fail within the first year. RECENT FINDINGS: In this review, we evaluate risks and benefits of MMC as an adjuvant for GFS. In addition, we discuss possible improvements of its use by adjusting dose and method of administration. SUMMARY: One way of improving GFS outcome is to prolong MMC delivery by using a drug delivery system.

Safety and Long-term Scleral Biomechanical Stability of Rhesus Eyes after Scleral Cross-linking by Blue Light.

Purpose: To assess the safety and long-term scleral biomechanical stability of rhesus eyes after blue light scleral CXL by investigating the biomechanical and microstructural changes.Methods: Seven rhesus monkeys (14 eyes) were observed in this study. All right eyes received blue light scleral CXL at the superior temporal equatorial sclera, and the left eyes served as controls. Biological ocular parameters were followed up to 1 year after scleral CXL. Stress-strain measurements of three rhesus sclera were measured, three rhesus retinas were examined histologically by H&E and TUNEL staining. And the microstructure of both the sclera and retina were observed by transmission electron microscopy at 1 year.Results: As for the retinal thickness, choroidal thickness, flow density of retinal superficial vascular networks and flash electroretinography (f-ERG) results, no significant differences were observed between the paired eyes at 1 year (P >.05). At the same time, the scleral collagen fibril distribution was much tighter, and the scleral biomechanical properties were significantly increased in the experimental eyes. However, apoptotic cells and retinal ultrastructural changes could still be found in the retina of the experimental eyes.Conclusion: This study demonstrates that blue light scleral CXL could effectively increase the scleral stiffness of the rhesus eye for at least 1 year, but ultrastructural change was still observed in the retina of scleral CXL eye. Therefore, the long-term intraocular safety of the blue light scleral CXL technique for preventing myopia progression should be investigated further.

Transscleral Iontophoresis for Noninvasive Ocular Drug Delivery of Macromolecules.

Purpose: The objectives were to investigate the effect of transscleral iontophoresis of macromolecules in vitro and in vivo, to study the importance of electroosmosis on macromolecules of low charge to mass ratio, and to evaluate transscleral iontophoresis efficacy in a choroidal neovascularization (CNV) animal model. Methods: Through in vitro transport experiments, the permeability coefficients of macromolecules [eg, immunoglobulin G (IgG), dextran 70 kDa] were determined under different conditions. The effect of ionic strength formulations and iontophoretic conditions was studied on the distribution of IgG and bevacizumab into the eye in vivo. Magnetic resonance imaging (MRI) was utilized to evaluate in vivo real time distribution of gadolinium-labeled albumin (Galbumin) following iontophoresis. The efficacy between no treatment, intravitreal injection (IVT), and iontophoresis of bevacizumab on a CNV model of subretinal injection of adeno-associated virus encoding human VEGF-165 was investigated. Results: The permeability data suggested a significant effect of ionic strength on the iontophoretic transport of macromolecules. Transscleral iontophoresis of IgG at 4 mA with a low ionic strength formulation was about 600 times greater than passive diffusion and 14-fold over a conventional formulation in vitro. Approximately 0.6 mg of bevacizumab can be delivered into the rabbit eye in vivo with a 20-min treatment of iontophoresis. MRI showed that Galbumin was in the posterior tissues after iontophoresis. In the CNV model, the iontophoresis and IVT methods of bevacizumab delayed retinal neovascularization by 4 and 8 weeks, respectively. Conclusions: Transscleral iontophoresis is capable of delivering macromolecule drugs through the conjunctiva and sclera, eventually exposing the retina/choroid to the drugs.

Differential Regional Stiffening of Sclera by Collagen Cross-linking.

Purpose: Corneal collagen cross-linking by ultraviolet light activation of riboflavin has been used clinically to enhance corneal stiffness. We sought to determine if cross-linking differentially affects scleral regions.Methods: Adjacent, parallel strips of sclera were cut from superolateral, superomedial, inferolateral, and inferomedial quadrants of posterior and equatorial sclera of 12 human cadaver eyes. One of each pair served as control while the other was cross-linked by immersion in 0.1% riboflavin and 365 nm exposure at 6 mW/cm2 irradiance for 30 min. Behavior of strips was characterized using a microtensile load cell. Preloaded strips were imaged using orthogonally mounted cameras and optical coherence tomography to determine specimen dimensions including cross-sectional area. Tension was measured during 0.1 mm/s constant rate elongation.Results: Young's modulus (YM), the slope of the relationship relating tensile stress to strain, was calculated at 8% strain, and increased significantly after cross-linking (P < .001). In posterior sclera, mean (± standard error of mean, SEM) YM is increased in the superolateral, superomedial, inferolateral, and inferomedial quadrants by 46 ± 15%, 32 ± 11%, 67 ± 20%, and 53 ± 11%, respectively. In equatorial sclera, YM is increased by 139 ± 43%, 68 ± 27%, 143 ± 92%, and 68 ± 14%, respectively. The YM of pooled equatorial quadrants increased significantly more than that of the pooled posterior quadrants.Conclusions: Scleral collagen cross-linking by ultraviolet activation of riboflavin differentially increases scleral YM more in the equatorial than posterior sclera, and most in the lateral, equatorial sclera. Cross-linking might be used to arrest progressive myopia or to prevent staphyloma formation.

Corneal and Scleral Problems Caused by Skin-Lightening Creams.

PURPOSE: To present a case series of patients with corneal and scleral changes associated with the use of skin-lightening creams. This is the first report of corneal changes with these widely available creams. METHODS: Three patients of West African origin presented with strikingly similar skin, corneal, and scleral changes and were found to have all been using skin-lightening creams containing hydroquinone. Histopathology was obtained for 1 patient. RESULTS: Three patients were referred to the corneal clinics of 2 hospitals with corneal changes and a history of blurred vision for 1 to 3 years. There was a 60-year-old woman from Nigeria and a 68-year-old woman and a 73-year-old man both from Ghana. All 3 had been using skin-lightening lotions containing hydroquinone on their faces for between 3 and 15 years and had black-blue facial pigmentation of exogenous ochronosis, a recognized complication of these creams. Their corneas all had horizontal striae radiating across the posterior corneas with scleral thinning and plaques. Linear brown epithelial pigmentation was observed within the lower third of the corneas. Biopsy of the sclera in 1 patient showed ochronosis. CONCLUSIONS: We present previously unreported eye changes associated with the use of skin-lightening creams containing hydroquinone, with a triad of signs: posterior corneal striae radiating from 3 o'clock to 9 o'clock, thinning and plaques in the sclera, and a normal endothelial cell count. Similar pathological changes are seen in exogenous ochronosis, a recognized skin complication of hydroquinone, are seen in the sclera.

Early Changes of Ocular Biological Parameters in Rhesus Monkeys After Scleral Cross-linking With Riboflavin/Ultraviolet-A.

PURPOSE: To evaluate the ocular biological parameter difference between scleral corneal cross-linking (CXL) and control eyes in rhesus monkeys by using a rebound tonometer, A-scan ultrasonography, retinoscopy, optical coherence tomography, and electroretinography (ERG). METHODS: Six rhesus monkeys were used in this study, with ages ranging from 3 to 3.5 years. One eye of each rhesus monkey was randomly selected to receive riboflavin/ultraviolet-A CXL in the temporal quadrant of the equatorial sclera and the contralateral eye served as an intra-individual control. The ocular biological parameters were repeatedly measured in both eyes of the monkeys before scleral CXL and 1 week, 1 month, and 3 months postoperatively. RESULTS: The intraocular pressure, refractive state, total axial length, and axial dimensions of the anterior chamber, crystalline lens, vitreous chamber, and central corneal thickness were not statistically significantly different between the control and cross-linked specimens at the different time periods (each P > .05). No obvious changes in the waveform of the standard full-field ERGs were observed in the control and cross-linked specimens. There were no statistically significant differences between the control and cross-linked specimens in the dark-adapted 0.01 ERG, the dark-adapted 3.0 ERG, the light-adapted 3.0 ERG, and the amplitudes of the a-wave and b-wave for the different time periods (each P >.05). CONCLUSIONS: The scleral CXL laboratory technique might not significantly affect the ocular biological parameters of the rhesus monkey in the early postoperative period, but long-term effects and histological changes still need to be investigated further. [J Refract Surg. 2019;35(5):333-339.].

Augmented Subscleral Trabeculectomy With Beta Radiation and Mitomycin C in Egyptian Glaucoma Patients.

PURPOSE: Subscleral trabeculectomy is the most common surgical treatment for glaucoma. However, wound healing and scar formation may result in bleb fibrosis, leading to bleb failure. The healing response of the wound is reported to be the single most important risk factor in determining the final intraocular pressure (IOP) after glaucoma filtration surgery. Thus, we aimed to evaluate the effect of preoperative beta irradiation and intraoperative mitomycin C (MMC) treatment as combined adjuncts to subscleral trabeculectomy in the management of glaucoma in Egyptian patients. PATIENTS AND METHODS: This prospective, interventional, comparative masked clinical study was performed between October 2016 and January 2018. This study included 50 subjects, 25 of whom underwent trabeculectomy augmented by MMC intraoperatively and beta radiation preoperatively at the bleb area (patient group #1). The remaining 25 subjects underwent trabeculectomy with MMC alone (control group #2). Beta radiation was administered 5 to 7 days before the surgery as a single dose (1000 cGy) using a strontium-90 probe. MMC (0.2 mg/mL) was administered for 2 minutes. RESULTS: There was a statistically significant difference in postoperative IOP between the groups from the second week. Intraoperative hyphema occurred in 6 cases in the control group #2, whereas no intraoperative hyphema was observed in patient group #1; this difference was statistically significant. CONCLUSIONS: Subscleral trabeculectomy augmented by beta radiation and MMC gives greater control over IOP. Therefore, we recommend using beta radiation before trabeculectomy in patients who may have a high risk of developing conjunctival fibrosis.

Genipin-Crosslinked Donor Sclera for Posterior Scleral Contraction/Reinforcement to Fight Progressive Myopia.

Purpose: Myopia has become a global public health problem, particularly in East Asia where myopic retinopathy has become one of the leading causes of blindness and visual impairment in the elderly population. The purpose of this study was to evaluate the efficacy of posterior scleral contraction/reinforcement (PSCR) surgery on controlling the progressive elongation of axial length of highly myopic eyes in young patients. Methods: This is a prospective self-controlled interventional case series. Forty young patients (<18-years old) with progressive high myopia received PSCR with a genipin-crosslinked donor scleral strip for one eye and the fellow eye served as concurrent control without surgery. The main outcome measurement was the change of axial length over 2 to 3 years of follow-up. Results: Immediately after the surgery, axial length was shortened and subsequently increased by 0.32 mm over the follow-up period. In contrast, axial length of the fellow eyes increased by 0.82 mm over the same period (P < 0.001, paired t-test). PSCR delayed axial elongation in eyes with or without staphyloma. No significant change of visual acuity, cornea refractive power, or retina thickness was noted between the surgery and fellow eyes. None of the patients lost visual acuity compared with the baseline. The procedure was well tolerated with only temporary corneal refractive axis shifts that recovered by the 6-month postsurgical visit. Conclusions: PSCR with genipin-crosslinked sclera is safe and effective to restrain eye globe elongation in young patients within a 2- to 3-year follow-up period.

Posterior scleral reinforcement using genipin-cross-linked sclera for macular hole retinal detachment in highly myopic eyes.

BACKGROUND/AIMS: To investigate the surgical outcomes of posterior scleral reinforcement (PSR) using genipin-cross-linked sclera to treat macular hole retinal detachment (MHRD) in highly myopic eyes. METHODS: Nineteen patients with high myopia (19 eyes) with MHRD were treated sequentially with genipin-cross-linked PSR and were followed at least for 1 year after the surgery. The best corrected visual acuity (BCVA), axial length (AL), optical coherence tomography (OCT) outcomes and the complications were evaluated. RESULTS: Macular hole was closed in 73.7% of the eyes, foveal reattachment rate was 100%. The mean logMAR BCVA improved from 1.27±0.55 preoperatively to 0.88±0.55 postoperatively. The preoperative AL (29.88±1.97 mm) was decreased (27.73±1.84 mm) after the operation (p<0.001). CONCLUSIONS: For at least a 1-year period of follow-up, PSR with genipin-cross-linked sclera should be considered as a preferred surgical approach to treat MHRD in highly myopic eyes, especially when foveal retinoschisis is also documented.

Results of an Adaptive Surgical Approach for Managing Late Onset Hypotony After Trabeculectomy With Mitomycin C.

OBJECTIVES: The objective of this study is to investigate the results of an adaptive approach of bleb revision surgery for late onset hypotony after trabeculectomy with mitomycin C because of bleb leakage and/or scleral melting. METHODS: A total of 29 eyes of 27 patients, aged 63.8±11.7 years with hypotony maculopathy [intraocular pressure (IOP), ≤6 mm Hg] because of late onset bleb leakage and/or scleral melting after trabeculectomy with mitomycin C in which minimally invasive transconjunctival suturing of the scleral flap was impossible were enrolled in this retrospective interventional case series. External bleb leakage was seen in 16 eyes, 11 eyes suffered from scleral melting. Because of the intraoperative findings regarding appearance of conjunctiva and sclera 4 different surgical approaches were used: (1) bleb excision (in case of external leakage) and conjunctival reapproximation, (2) bleb excision and free conjunctival autografting, (3) human donor scleral patch grafting (in case of scleral flap defect) with conjunctiva reapproximation and (4) combined conjunctival and scleral patch grafting. Outcome measures were IOP and visual acuity (VA) development over time. Data analysis comparing changes in the parameters (IOP and VA) before and after bleb revision surgery was carried out using the paired t test. RESULTS: Changes in IOP and VA were analyzed over 9.3±8.3 months (range, 1.1 to 36.5 mo). IOP increased from 4.0±1.8 mm Hg, (P<0.001) before revision surgery to 13.1±4.1 mm Hg at 3 months after revision and 12.6±3.8 mm Hg at last follow-up visit, showing no significant difference in IOP between 3 months post revision and at the last documented patients' follow-up visit (P=0.28). The VA before revision surgery (0.42±0.28 logMAR) significantly increased (P=0.05) 3 months after revision (0.32±0.23 logMAR) and remained stable (P=0.65) until the last follow-up visit (9.3±8.3 mo; range, 1.1 to 36.5) (0.35±0.32 logMAR). CONCLUSIONS: In patients with hypotony an adaptive approach of bleb management shows good results both in terms of IOP control and improvement in VA.

Clinical Outcomes and Intraocular Pressure Control After Scleral-glued Intraocular Lens Insertion in Eyes With Pseudoexfoliation.

PURPOSE: To analyze clinical outcomes and intraocular pressure control following scleral-glued intraocular lens (IOL) fixation in eyes with pseudoexfoliation (PXF). METHODS: A retrospective chart review and outcome analysis was performed on a series of eyes undergoing glue-assisted, scleral-fixated (scleral-glued) IOL insertion in the setting of PXF and poor or absent capsular support. RESULTS: In total, 28 eyes were included in the study. The indications for scleral-glued IOL fixation included late endocapsular IOL dislocation (21/28, 75%), exchange for iris-fixated IOL due to complication (4/28, 14%), subluxed crystalline lens (2/28, 7%), and aphakia after complicated cataract surgery (1/28, 4%). In total, 15/28 (54%) eyes had diagnosed preexisting glaucoma at the time of scleral-glued surgery. The most common postoperative complication was ocular hypertension requiring escalation of medical management, which occurred in 8/28 (29%) eyes. At final follow-up, corrected distance visual acuity was equivalent to or improved from preoperative measurements in 25/28 (89%) eyes. CONCLUSIONS: The scleral-glued surgery is a good option for fixating an IOL in eyes with PXF and poor zonular integrity or absent capsular support. Special attention should be placed on intraocular pressure control following surgery, which can be less predictable in PXF eyes with or without preexisting glaucoma.

Riboflavin and ultraviolet A irradiation for the prevention of progressive myopia in a guinea pig model.

In this study, we evaluated the effect of oral administration of riboflavin combined with whole-body ultraviolet A (UVA) irradiation on the biochemical and biomechanical properties of sclera in a guinea pig model to control the progression of myopia. Experimental groups were administered 0.1% riboflavin solution with or without vitamin C by gavage from 3 days before myopic modeling and during the modeling process. Guinea pigs underwent 30 min of whole-body UVA irradiation after each gavage for 2 weeks. For control groups, guinea pigs were administered vitamin C and underwent either whole-body UVA irradiation without 0.1% riboflavin solution or whole-body fluorescent lamp irradiation with or without 0.1% riboflavin solution. Resultantly, myopia models were established with an increased axial length and myopic diopter. Compared with myopic eyes in the control groups, the net increase in axial length, diopter and strain assessment decreased significantly, and the net decrease in sclera thickness, ultimate load, and stress assessment decreased significantly in experimental groups. MMP-2 expression showed a lower net increase, while TIMP-2 expression showed a lower net decrease. In addition, hyperplasia of scleral fibroblasts was more active in myopic eyes of experimental groups. Overall, our results showed that oral administration of riboflavin with whole-body UVA irradiation could increase the strength and stiffness of sclera by altering the biochemical and biomechanical properties, and decreases in axial elongation and myopic diopter are greater in the guinea pig myopic model.

Management of necrotizing scleritis after pterygium surgery with rituximab.

The authors present a case of necrotizing scleritis after pterygium excision successfully treated with rituximab after attempts with high doses of corticosteroids and immunosuppressive drugs. A literature review revealed case reports and a phase I/II dose-ranging randomized clinical trial using rituximab for necrotizing scleritis with or without association with autoimmune disease. This is the only case report on rituximab treatment for necrotizing scleritis after pterygium surgery. In cases with refractoriness to immunosuppressive drugs, a CD20 antibody can be used.

Scleral Cross-Linking Using Riboflavin UVA Irradiation for the Prevention of Myopia Progression in a Guinea Pig Model: Blocked Axial Extension and Altered Scleral Microstructure.

PURPOSE: To develop methods of collagen cross-linking (CXL) in the sclera for the treatment of progressive myopia and to investigate the biomechanical and histological changes that occur in as a result. METHODS: Twenty 14-day-old guinea pigs were divided into 3 groups: the cross-linking group (CL, n = 8), non cross-linking group (NCL, n = 8), and control group (n = 4). The scleras of the right eyes of the guinea pigs in the CL group were surgically exposed and riboflavin was dropped onto the irradiation zone for 20 seconds prior to ultraviolet-A (UVA) irradiation. The same procedure was conducted on the NCL group but without UVA irradiation. No procedure was conducted on the control group. The right eyes of the guinea pigs in the CL and NCL groups were then fitted with -10.00DS optics for six weeks. Retinoscopy and the axial lengths (AXL) were measured at baseline, and at the second, fourth and sixth weeks post-treatment in all three groups. All animal subjects were euthanized after the sixth week and then biomechanical and histopathological examinations of the scleras were conducted. RESULTS: The mean AXL of the NCL group was longer than both the control and CL groups at six weeks (P = 0.001). The mean refractive error in the NCL group was statistically significantly more negative than both the control and the CL groups at six weeks (P = 0.001). The scleral collagen fiber arrangements of the CL and control groups were denser and more regularly distributed than the NCL group. Ultimate stress of the sclera was lowest in the NCL group, followed by the CL then the control group (P<0.05). Ultimate strain (%) of the sclera was lowest in the CL group followed by the NCL and then the control group (P<0.05). CONCLUSION: Our study demonstrates that scleral CXL using riboflavin UVA irradiation effectively prevents the progression of myopia by increasing scleral biomechanical strength in a guinea pig model.

Management of necrotizing scleritis after pterygium surgery with rituximab / Tratamento com rituximabe de esclerite necrosante após cirurgia de pterigeo

ABSTRACT The authors present a case of necrotizing scleritis after pterygium excision successfully treated with rituximab after attempts with high doses of corticosteroids and immunosuppressive drugs. A literature review revealed case reports and a phase I/II dose-ranging randomized clinical trial using rituximab for necrotizing scleritis with or without association with autoimmune disease. This is the only case report on rituximab treatment for necrotizing scleritis after pterygium surgery. In cases with refractoriness to immunosuppressive drugs, a CD20 antibody can be used.

RESUMO Os autores apresentam um caso de sucesso no tratamento com rituximabe de esclerite necrosante após cirurgia de pterígio refratário a altas doses de corticosteroides e drogas imunossupressoras. Uma revisão da literatura direcionada ao uso de rituximabe para tratamento de esclerites necrosantes revelou relatos de casos e um estudo clínico randomizando fase I/II. Este é o único caso descrito de rituximabe para o tratamento de esclerite necrosante pós cirúrgica. O uso de anticorpo anti-CD20 pode ser uma opção em casos refratários aos imunossupressores no tratamento da esclerite necrosante pós-cirúrgica.

Episcleral drug film for better-targeted ocular drug delivery and controlled release using multilayered poly-ε-caprolactone (PCL).

UNLABELLED: Triamcinolone acetonide (TA) and poly-ε-caprolactone (PCL) were engineered into a micro drug film for episcleral application to better manage chronic vitreoretinal diseases such as proliferative vitreoretinopathy (PVR). Compared to an intravitreal drug injection, this drug film is much safer without breaking into ocular barriers. Compared to a traditional subtenon injection, this drug film demonstrated superior therapeutic duration, better drug bioavailability in the choroid and retina, and better-targeted drug delivery ability. The rabbit eye study demonstrated that using the PCL-TA film led to 5.6 and 3.4 times higher drug AUC in the choroid and the retina respectively than in eyes following a subtenon drug injection. The mean drug residence time in the rabbit choroid was also doubled by using the episcleral TA film (86days versus 43days). Remaining TA in the drug film was consistently higher than that in the subtenon space, indicating controlled release of TA by the PCL-TA film. The pharmacokinetics of triamcinolone in the choroid and retina were optimized from typical first-order kinetics to a more sustained release by use of this film. This episcleral film system worked better on rabbit eyes than on guinea pig eyes, indicating that scleral thickness and eye size may be crucial aspects to consider when choosing an animal model or when designing a transscleral delivery device for human use. This engineered drug film may be very useful in preventing and managing PVR associated with open globe trauma or surgical repair for retinal detachment. STATEMENT OF SIGNIFICANCE: This study demonstrated a novel micro episcleral drug film that is made from the engineering of triamcinolone acetonide (TA) into poly-ε-caprolactone (PCL). The film can be conveniently placed at the injury or disease site during primary surgery and provide controlled release of TA for four months that covers the high-risk time window for developing proliferative vitreoretinopathy (PVR). This engineered drug film may be very useful in preventing and managing PVR associated with open globe trauma or intraocular surgery.

A Biological Tissue Adhesive and Dissolvent System for Intraocular Tumor Plaque Brachytherapy.

PURPOSE: To examine a novel technique for simplified placement and removal of plaque brachytherapy by fibrin glue and urokinase (medac Gmbh, Hamburg, Germany). MATERIALS AND METHODS: In six enucleated porcine eyes, plaques were placed on the episclera and fibrin glue was applied to cover it. Urokinase was used to dissolve the glue in three eyes and saline was used in three eyes. Adhesion strength was measured further on 15 plaques affixed to porcine eyes (glued in five with intact conjunctiva, glued in five with removed conjunctiva, and sutured in five). RESULTS: Saline had no effect on the glue-plaque-eye complex, whereas the urokinase (0.38 mL ± 0.08 mL) easily dissolved the adhesion between the glue layer and surrounding tissues. The weight required to detach the plaques was 0.349 kg ± 0.173 kg for glued eyes with intact conjunctiva, 0.405 kg ± 0.083 kg for sutured eyes (P = .59), and 0.032 kg ± 0.004 kg for glued eyes without intact conjunctiva (P ≤ .015). CONCLUSIONS: The usage of the biological adhesive and dissolvent system was applicable for plaque surgery in an ex vivo animal model.