Hydrogel-Based Oxygen and Drug Delivery Dressing for Improved Wound Healing.

Herein, we propose a Carbopol hydrogel-based oxygen nanodelivery "nanohyperbaric" system as a wound dressing material for an enhanced wound healing process. Oxygen nanobubbles (ONBs) were used to supply oxygen, and collagenase was added in the gel as a drug model. Both oxygen and collagenase would benefit the wound healing process, and the Carbopol hydrogel serves as the matrix to load ONBs and collagenase in the wound dressing. The obtained ONB-embedded Carbopol hydrogel with collagenase (ONB-CC) could provide 12.08 ± 0.75 µg of oxygen from 1 mL of ONB-CC and exhibited a notable capacity to prolong the oxygen holding for up to 3 weeks and maintained the enzymatic activity of collagenase at more than 0.05 U per 0.1 mL of ONB-CC for up to 17 days. With HDFa cells, the ONB-CC did not show a notable effect on the cell viability. In a scratch assay, the oxygen from ONBs or collagenase aided cell migration; further, the ONB-CC induced the most obvious scratch closure, indicating an improvement in wound healing as a cocktail in the ONB-CC. The mRNA expression further demonstrated the effectiveness of the ONB-CC. Studies in rats with punched wounds treated with the ONB-CC dressing showed improved wound closure. Histopathological images showed that the ONB-CC dressing enhanced re-epithelization and formation of new blood vessels and hair follicles. The proposed ONB-CC has excellent potential as an ideal wound dressing material to accelerate wound healing by integration of multiple functions.

Use of Adjunctive Corticosteroid With Antivascular Endothelial Growth Factor Agents in the Treatment of Choroidal Neovascular Membrane Associated With Presumed Ocular Histoplasmosis.

Purpose: To evaluate the impact of combination treatment of antivascular endothelial growth factor (anti-VEGF) intravitreal injections and corticosteroids in patients with choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS). Methods: A retrospective multicenter study was conducted in a cohort from Illinois and Missouri. Patients were identified over an 8-year period, and data were evaluated over a 1-year study window commencing with treatment initiation. Group 1 included patients treated with intravitreal injections of anti-VEGF, and group 2 included those who received intravitreal injections of anti-VEGF and adjuvant corticosteroids. Optical coherence tomography (OCT) measurements and increases in Early Treatment Diabetic Retinopathy Study (ETDRS) letter score were compared between each group. Results: Using the method of last visit carried forward, the visual acuity (VA) in group 2 was 6.42 ETDRS letters better than the VA in group 1 at the final assessment. Patients in group 2 had a mean ETDRS letter gain of 21.50 (P = .06) from the initial baseline vision. The average amount of decrease in OCT central subfield thickness compared with baseline was lower in group 1 (80.9 ± 129.8 µm) vs group 2 (102.8 ± 90.40 µm) at the 1-year follow-up visit (P = .25). Conclusions: Approved treatment of CNV secondary to POHS is limited. Adjuvant corticosteroid treatment in patients with CNV secondary to POHS may provide better long-term vision and OCT outcomes than anti-VEGF alone and may offer an additional therapy option for these patients.

Oxygen Nanobubbles-Embedded Hydrogel as Wound Dressing to Accelerate Healing.

Herein, we propose an oxygen nanobubbles-embedded hydrogel (ONB-G) with carbopol for oxygenation of wounds to accelerate the wound healing process. We integrate carbopol, hydrogel, and dextran-based oxygen nanobubbles (ONBs) to prepare ONB-G where ONBs can hold and release oxygen to accelerate wound healing. Oxygen release tests showed that the proposed ONB-G could encapsulate oxygen in the hydrogels for up to 34 days; meanwhile, fluorescence studies indicated that the ONB-G could maintain high oxygen levels for up to 4 weeks. The effect of carbopol concentration on the oxygen release capacity and rheological features of the ONB-G were also investigated along with the sterility of ONB-G. HDFa cell-based studies were first conducted to evaluate the viability, proliferation, and revival of cells in hypoxia. Scratch assay and mRNA expression studies indicated the potential benefit for wound closure. Histological evaluation of tissues with a pig model with incision and punch wounds showed that treatment with ONB-G exhibited improved healing compared with hydrogel without ONBs or treated without the gel. Our studies show that dextran-shell ONBs embedded in a gel (ONB-G) have the potential to accelerate wound healing, given its oxygen-holding capacity and release properties.

Characterization of Oxygen Nanobubbles and In Vitro Evaluation of Retinal Cells in Hypoxia.

Purpose: Vein or artery occlusion causes a hypoxic environment by preventing oxygen delivery and diffusion to tissues. Diseases such as retinal vein occlusion, central retinal artery occlusion, or diabetic retinopathy create a stroke-type condition that leads to functional blindness in the effected eye. We aim to develop an oxygen delivery system consisting of oxygen nanobubbles (ONBs) that can mitigate retinal ischemia during a severe hypoxic event such as central retinal artery occlusion. Methods: ONBs were synthesized to encapsulate oxygen saturated molecular medical grade water. Stability, oxygen release, biocompatibility, reactive oxygen species, superoxide, MTT, and terminal uridine nick-end labeling assays were performed. Cell viability was evaluated, and safety experiments were conducted in rabbits. Results: The ONBs were approximately 220 nm in diameter, with a zeta potential of -58.8 mV. Oxygen release studies indicated that 74.06 µg of O2 is released from the ONBs after 12 hours at 37°C. Cell studies indicated that ONBs are safe and cells are viable. There was no significant increase in reactive oxygen species, superoxide, or double-stranded DNA damage after ONB treatment. ONBs preserve mitochondrial function and viability. Histological sections from rabbit eyes indicated that ONBs were not toxic. Conclusions: The ONBs proposed have excellent oxygen holding and release properties to mitigate ischemic conditions in the retina. They are sterile, stable, and nontoxic. Translation Relevance: ONB technology was evaluated for its physical properties, oxygen release, sterility, stability, and safety. Our results indicate that ONBs could be a viable treatment approach to mitigate hypoxia during ischemic conditions in the eye upon timely administration.

Ratiometric Analysis of In Vivo Optical Coherence Tomography Retinal Layer Thicknesses for Detection of Changes in Alzheimer's Disease.

We analyzed ophthalmic retinal optical coherence tomography (OCT) images from patients with Alzheimer's disease (AD) to identify retinal layer thickness and ratio changes that may serve as image-based biomarkers for the disease. One three-dimensional volume before and one after diagnosis for each of 48 patients were segmented to identify retinal layer and total retinal thicknesses. Between before- and after-diagnosis retinal OCT images, there were significant thickness changes in six of ten (60%) retinal layers across all 48 patients. Through a comparison with age-matched healthy subjects, the significant changes were attributed to AD only (NFL and PR2 layers), age only (GCL, IPL, and RPE layers), or both AD and age (OPL layer). Analyzing ratios of retinal layer thicknesses, 53 of 90 (58.89%) ratios had significant changes. The four independently non-significant layers were assessed to be affected by neither AD nor age (INL layer) or both AD and age (ELM, PR1, and BM layers). The demonstrated image segmentation, measurement, and ratiometric analysis of retinal layers in AD patients may yield a noninvasive OCT image-based retinal biomarker that can be used to detect retinal changes associated with this disease.

Anatomical and Functional Outcomes of Relaxing Parafoveal Nasal Retinotomy for Refractory Macular Hole Repair.

Purpose: This work aimed to assess postoperative outcomes associated with relaxing parafoveal nasal retinotomy for refractory macular hole repair. Methods: This was a retrospective interventional study of patients with persistent or recurrent macular holes following 1 or more standard repair procedures with pars plana vitrectomy and internal limiting membrane peeling. Patients received an additional pars plana vitrectomy and relaxing parafoveal nasal retinotomy, followed by fluid-air and air-gas exchange. Key postoperative outcomes included the achievement of macular hole closure and changes in visual acuity from baseline. Results: Thirteen patients with refractory macular holes were included, with a median age of 65 years (range, 49-90 years). The aperture diameter of the 13 macular holes ranged from 180 to 799 µm (median, 538 µm). Vitrectomy and relaxing parafoveal nasal retinotomy were performed in all 13 eyes, and after a median follow-up of 12 months (range, 3-34 months), anatomical closure was achieved in 12 of 13 eyes (92.3%). Overall, visual acuity (mean ± SE) improved significantly from 1.20 ± 0.15 logMAR (approximate Snellen equivalent, 20/320) at baseline to 0.84 ± 0.11 logMAR (Snellen, ∼ 20/125) during postoperative follow-up (P < .05). Central and paracentral scotomas were observed in 8 of 11 eyes with postoperative Humphrey visual field 10-2 and/or 24-2 data available. Conclusions: Relaxing parafoveal nasal retinotomy may be an effective method to promote anatomical closure and improve vision outcomes in patients with recalcitrant macular holes.

An Atypical Presentation of Propionibacterium Acnes Endophthalmitis Following Cataract Surgery.

Purpose: To describe a case with an unusual presentation of Propionibacterium acnes (P acnes) with ultimately a good visual outcome. Methods: A case report with review of approaches to P acnes endophthalmitis. Results: We describe a patient with an unusual presentation of P acnes of panuveitis with white, circular preretinal lesions without intracapsular deposits. Diagnosis was made from cultures from pars plana vitrectomy. Eventually, she was definitively managed with capsulectomy, repositioning of her intraocular lens via sutureless intrascleral fixation, and intravitreal vancomycin injection. Conclusion: This is a report of P acnes endophthalmitis presenting with discrete preretinal lesions where surgical and medical management lead to a complete resolution of uveitis and symptoms after a 3-year follow up where the patient's final visual acuity was Snellen 20/20 OU.

A Case of Unilateral Optic Neuropathy Following Influenza Vaccination.

The influenza vaccination has greatly benefited public health, leading to significant reductions in flu season hospitalizations and deaths. However, with more widespread administration of this vaccine, it is expected that the absolute number of patients that present with unusual, adverse reactions will increase. Here, we report a case of a 55-year-old woman who developed a progressive optic neuropathy and severe visual loss associated with optic disc edema following influenza virus vaccination. Our patient also experienced other concurrent symptoms, including bilateral knee effusions, muscle spasms and a facial rash. The strong temporal connection between the vaccine administration and the development of sequelae suggests that the optic neuropathy was an adverse reaction. Furthermore, HLA typing of our patient revealed alleles that have been linked to autoimmune reactions, consistent with the notion that specific HLA alleles could be involved in the pathophysiology of these adverse reactions.

Comparative evaluation of no dye assistance, indocyanine green and triamcinolone acetonide for internal limiting membrane peeling during macular hole surgery.

PURPOSE: To evaluate the anatomical closure rate and visual outcome in patients undergoing pars plana vitrectomy with internal limiting membrane peeling without dye enhancement and with indocyanine green or triamcinolone acetonide assistance. METHODS: This is a retrospective, comparative interventional case series. The electronic charts of 435 eyes of 415 patients with idiopathic macular holes who underwent macula hole surgery were reviewed from January 2003 to April 2010. The patients were assigned to 3 groups: no dye assistance (Group 1), indocyanine green-assisted (Group 2), and triamcinolone acetonide-assisted internal limiting membrane peel (Group 3). The data were recorded for 3-, 6-, and 12-month follow-up visits. Main outcome measures were postoperative visual acuity and macular hole closure. RESULTS: The overall macular hole closure rate with a single surgery was 94.7% (108 of 114). In Group 1: 91.4% (191 of 209), in Group 2: 94.1% (112 of 119), and in Group 3: 95.9% (93 of 97) achieved closure. Closure rate for holes that were ≤400 µm in diameter was 98.8% compared with >400 µm, which was 90.4% (P = 0.001). There was a statistically significant (P < 0.001) improvement from preoperative visual acuity to postoperative visual acuity in all groups across all time points. There was no statistically significant visual acuity difference among three groups. At 12-month follow-up, 77.7% in Group 1, 66.1% in Group 2, and 81.3% in Group 3 achieved 20/50 visual acuity or better. CONCLUSION: The study shows that good anatomical and functional results can be achieved with no dye and with indocyanine green or triamcinolone acetonide dye assistance for internal limiting membrane peeling during macular hole surgery. Overall, visual acuity levels did not differ among groups, although subanalysis of the results suggests subtle indocyanine green toxicity.

Clinical and image-guided chorioretinal findings in long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency.

The purpose of this study is to report clinical, optical coherence tomography (OCT), and fluorescein angiogram/indocyanine green angiography (FA/ICG) findings in patients with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) enzyme deficiency in two siblings. A 13-year-old girl and her 14-year-old brother presented with progressive decrease in central vision. Clinically, there were blond-looking fundi, diffuse retinal pigment epithelial (RPE) disruption/atrophy in the macula and peripheral retina with choriocapillaris atrophy in both of them. OCT showed RPE irregularity and diffuse disruption of the RPE layer. FA/ICG imaging demonstrated transmitted choroidal fluorescence secondary to diffuse RPE atrophy with no evidence of leakage. Electroretinogram and electrooculogram findings were suggestive of primary abnormality of pigment epithelium. The boy died of cardiac/respiratory illness, whereas his sister is alive at the last follow-up. Abnormal chorioretinal findings in LCHAD patients should be carefully followed. Regular follow-up is recommended to monitor the ocular and systemic status.

Oscillatory photodynamic therapy for choroidal neovascularization and central serous retinopathy; a pilot study.

PURPOSE: To report the preliminary results of oscillatory photodynamic therapy (OPDT) for choroidal neovascularization (CNV) and central serous retinopathy (CSR). METHODS: This study included 7 eyes of 6 patients with CSR (2 eyes), idiopathic CNV (2 eyes), CNV due to age-related macular degeneration (AMD) (2 eyes), and peripapillary CNV secondary to presumed ocular histoplasmosis syndrome (1 eye). Intravenous verteporfin (6 mg/m(2) body surface area) was infused over 10 minutes followed by oscillating laser (wavelength 689 nm) covering slightly beyond the entire lesion. An Area Centralis lens was applied and laser was delivered (600 mW/cm(2) fluence rate and 50 J/cm(2) dose). Intravitreal bevacizumab and dexamethasone combination therapy was used with OPDT in 4 eyes with CNV; intravitreal dexamethasone and triamcinolone acetonide were injected in the other eye with CNV. Clinical examination, funduscopy, fluorescein angiography, and optical coherence tomography (OCT) were performed at baseline and after treatment. RESULTS: After mean follow-up of 7.1±5.1 months, visual acuity improved from 0.87±0.69 logMAR (20/160) to 0.60±0.65 logMAR (20/80) (P = 0.027); central foveal thickness decreased from 322±62.1 to 240.7±34.8 microns as measured by OCT (P = 0.018). Fluorescein angiography and OCT demonstrated cessation of vascular leakage, and resolution of hemorrhage and subretinal fluid in all eyes. No adverse events or recurrence were noted. CONCLUSION: OPDT was effective in treating CNV lesions and CSR. OPDT may be an improvement on standard PDT due to reduced side effects, thermal damage and scarring.

Photodynamic therapy of choroidal hemangioma in sturge-weber syndrome, with a review of treatments for diffuse and circumscribed choroidal hemangiomas.

We report three new cases of patients with Sturge-Weber Syndrome and symptomatic retinal detachments from diffuse choroidal hemangiomas successfully treated with photodynamic therapy (PDT) and review medical literature on the available treatment options for choroidal hemangiomas. All patients were treated with a single session of PDT with verteporfin infused at a concentration of 6 mg/m(2) and treated for 83 seconds with 689-nm Zeiss laser that was delivered with total energy level of 50 J/cm(2) with an intensity of 600 mW/cm(2). The exudative retinal detachment (RD) and macular edema completely resolved in all cases by 1-4 months after PDT treatment. Visual acuity improved in all three cases with diminished tumor size in the areas of treatment. One case was followed for 5 months, another for 2 years, and the third case for 6 years, with no recurrence of exudative RD. PDT is an effective treatment option for visual deterioration from exudative retinal detachment in patients with diffuse choroidal hemangiomas.

Regression of peripapillary choroidal neovascularization after oscillatory transpupillary thermotherapy and anti-VEGF pharmacotherapy.

PURPOSE: We prospectively evaluated a new treatment for recalcitrant choroidal neovascularization (CNV) in 4 patients. We used an infrared laser (810 nm) in oscillatory thermotherapy (OTT) mode combined with indocyanine green (ICG) dye, utilizing the beneficial effect of both thermotherapy and photodynamic therapy. We describe preliminary experiences with ICG-assisted OTT (I-OTT) combined with intravitreal bevacizumab/dexamethasone for refractory peripapillary CNV resistant to standard therapy. METHODS: Clinical examination, funduscopy, fluorescein angiography, and optical coherence tomography were performed at baseline and postoperatively. Infrared laser spot size was approximately one-half the lesion size (oscillation 2-3 Hz). Intravitreal injections of bevacizumab (1.25 mg) and dexamethasone (1000 µg) were done during the same visit. RESULTS: Mean follow-up was 12.5 months (range 5-17). Mean energy level was 325 mW (range 200-500) in oscillatory mode (2-3 Hz/sec) pre- and post-ICG infusion. Indocyanine green dose was approximately 1 mg/kg (75 mg/patient). All patients had a single treatment. Mean visual acuity improved in 1 patient from 20/60 to 20/30 and remained the same in the other 3 (20/20, 20/40, and 20/400). At final examination, there was no evidence of clinical or angiographic activity of CNV. CONCLUSIONS: Indocyanine green-assisted OTT has the potential to treat CNV in wet age-related macular degeneration. It may reduce thermal side effects and eliminate or reduce the need for frequent intravitreal treatment. We postulate that I-OTT has a synergistic effect of thermal energy combined with a weak photosensitizer (ICG) applied in an individualized manner, which minimizes thermal damage to retinal and choroidal tissue. Additional anti-vascular endothelial growth factor pharmacotherapy enhances the effect of I-OTT on abnormal new vessels.

Retinal artery occlusion and multiple retinal deposits as a consequence of therapeutic arteriovenous fistula embolization.

PURPOSE: To describe a rare case of a patient who underwent a therapeutic arteriovenous fistula embolization and developed painful vision loss in one eye and to describe the clinical course, present sequential images, and propose an explanation. METHODS: The record of one patient with subretinal deposits, including fundus photographs and fluorescein angiography, was reviewed. RESULTS: Fundus photographs show creamy white circumscribed subretinal deposits. Fluorescein angiography shows evidence of retinal and choroidal ischemia. CONCLUSION: This patient had anomalous anatomy with an ophthalmic artery arising from the middle meningeal artery. This allowed the embolic material to reflux into the ophthalmic circulation and deposit in the retinal and choroidal circulation, causing infarcts.

Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial).

BACKGROUND: Age-related macular degeneration (ARMD) is the leading cause of vision loss in aging Westem societies. The objective of the lutein antioxidant supplementation trial (LAST) is to determine whether nutritional supplementation with lutein or lutein together with antioxidants, vitamins, and minerals, improves visual function and symptoms in atrophic ARMD. METHODS: The study was a prospective, 12-month, randomized, double-masked, placebo-controlled trial conducted at an urban midwestern Veterans Administration Hospital from August 1999 to May 2001. Ninety patients with atrophic ARMD were referred by ophthalmologists at two Chicago-area veterans medical facilities. Patients in Group 1 received lutein 10 mg (L); in Group 2, a lutein 10 mg/antioxidants/vitamins and minerals broad spectrum supplementation formula (L/A); and in Group 3, a maltodextrin placebo (P) over 12 months. RESULTS: In Groups 1 L and 2 L/A, mean eye macular pigment optical density increased approximately 0.09 log units from baseline, Snellen equivalent visual acuity improved 5.4 letters for Group 1 L and 3.5 letters for Group 2 L/A, and contrast sensitivity improved. There was a net subjective improvement in Amsler grid in Group 1 L. VFO-14 questionnaires conceming subjective glare recovery were nearly significant at 4 months for Group 2 L/A. Patients who received the placebo (Group 3) had no significant changes in any of the measured findings. CONCLUSION: In this study, visual function is improved with lutein alone or lutein together with other nutrients. Further studies are needed with more patients, of both genders, and for longer periods of time to assess long-term effects of lutein or lutein together with a broad spectrum of antioxidants, vitamins, and minerals in the treatment of atrophic age-related macular degeneration.