Intra-operative optical coherence tomography in corneal lamellar graft reinforcement for Boston type I keratoprosthesis corneal melt.

Corneal melt is a sight-threatening complication of Boston type 1 keratoprosthesis (KPro). Severe corneal melt may result in hypotony, choroidal hemorrhage, and even spontaneous extrusion of the KPro, which may lead to a poor visual prognosis. Lamellar keratoplasty is one surgical option for the management of mild corneal melt, especially when a new KPro is not available. Herein, we present a new surgical technique application, intra-operative optical coherence tomography (iOCT) for the management of cornea graft melt after Boston type 1 KPro implantation. The visual acuity and the intra-ocular maintained stable at 6 months post-operatively, and the KPro remained in place without corneal melting, epithelial ingrowth, or infection. iOCT may prove to be a real-time, non-invasive, and accurate treatment for corneal lamellar dissection and suturing beneath the anterior plate of the KPro, which can effectively help the surgeon to make surgical decisions and reduce post-operative complications.

Clinical Experience in Patients with Ocular Burns Treated with Boston Type I Keratoprosthesis Implantation with or Without Prophylactic Ahmed Glaucoma Valve Implantation.

INTRODUCTION: To compare outcomes in eyes with ocular burns following Boston Type I keratoprosthesis (KPro) implantation with and without prophylactic pars plana tube surgery. METHODS: A retrospective review of patients with ocular burns who underwent KPro surgery at Zhongshan Ophthalmic Center was performed. Twenty-six eyes of 26 patients without a preoperative diagnosis of glaucoma before KPro surgery met the inclusion criteria. Preoperative glaucoma was defined as a history of a durable elevated intraocular pressure (IOP) ≥ 25 mmHg at different time points, which resulted in the introduction of anti-glaucoma medication or surgical intervention. Sixteen eyes underwent KPro alone (Group 1), and 10 eyes received KPro with prophylactic pars plana tube surgery (Group 2). RESULTS: Group 1 and Group 2 were similar in the proportions of the ocular burn type and preoperative clock hours of peripheral anterior synechiae by ultrasound biomicroscopy (1.88 ± 1.63 vs. 2.30 ± 1.83; P = 0.54). Before KPro surgery, 62.5% of eyes in Group 1 and 50.0% of eyes in Group 2 had intraocular surgeries (P = 0.53). The follow-up time was 18 months. At the final follow-up time, the two groups had similar visual acuity (1.34 ± 0.87 logMAR, 1.03 ± 0.71 logMAR; P = 0.35) and eyes with a C/D ratio ≥ 0.8 (7/16, 2/10; P = 0.21), but more eyes in Group 1 developed glaucoma de novo than eyes in Group 2 (62.5%, 20%; P = 0.04) and had undergone secondary glaucoma surgery after KPro implantation (7/16 vs. 0/10; P = 0.02). CONCLUSION: In eyes injured with ocular burns, KPro implantation with prophylactic pars plana tube surgery may be a feasible option to rehabilitate visual acuity and decrease the incidence of glaucoma de novo.

Treatment of Oculoplastic and Ocular Surface Disease in Eyes Implanted with a Type I Boston Keratoprosthesis in Southern China: A Retrospective Study.

INTRODUCTION: This study aimed to describe the clinical features, surgical management of the eyelid and ocular surface, and outcomes of 16 patients implanted with a Boston type I keratoprosthesis (KPro). METHODS: A retrospective, single-center, consecutive case series of 16 patients with Stevens-Johnson syndrome (1), ocular chemical burns (12), and ocular thermal burns (3) implanted with KPro was studied. All subjects were men aged 27-51 years. Surgical treatment and outcomes for eyelid malposition, symblepharon, and glaucoma were assessed. RESULTS: From September 2010 to February 2019, 29 patients were admitted to Zhongshan Ophthalmic Center for KPro implantation, of whom 16 (55%) required eyelid or ocular surface surgeries to maintain hydration and protect the corneal tissue, which is vulnerable to epithelial defects. Forty-one adnexal surgical procedures were performed. The most common indication for surgery was symblepharon, and the most frequent procedures were symblepharon lysis with ocular mucous membrane grafts and amniotic membranes (7) and full-thickness skin grafts to the eyelids (7). Preoperative conjunctival injection and corneal staining were documented in 9 (56%) and 8 (50%) eyes, respectively, and at up to 4 months postoperative follow-up (the last adnexal surgery before KPro) were recorded in 3 (19%, p = 0.03) and 2 (12%, p = 0.02) eyes, respectively. Glaucoma drainage devices were inserted in six patients. One patient with Stevens-Johnson syndrome underwent FP7 Ahmed glaucoma valve (AGV) implantation inferotemporally and developed plate exposure 2 months postoperatively. Five patients underwent FP8 AGV implantation with tube insertion into the vitreous cavity due to the scarred conjunctiva and limited subconjunctival space. In the study period, intraocular pressure (IOP) was in the normal range, and no tube or plate exposure was observed. CONCLUSION: The ocular environment is critical for successful KPro surgery. A multidisciplinary approach for any lid and ocular surface abnormality in ocular burns or Stevens-Johnson syndrome is important to improve the quality of the ocular surface and accommodate KPro and AGV, which is vital for maintaining vision after KPro surgery. FP8 AGV may be feasible for IOP control in adult KPro cases with restricted subconjunctival space.

Nd:YAG Laser for Ahmed Tube Shunt Blockage in Patients Implanted with Boston Type I Keratoprosthesis.

INTRODUCTION: The purpose of this study was to describe the results using the Nd:YAG laser to reopen blocked glaucoma tube shunts in three ocular chemical burn patients with Boston keratoprostesis type I (KPro) implantation. METHODS: The medical records of the three patients at Zhongshan Ophthalmic Centre were reviewed. RESULTS: Patient 1, who had glaucoma secondary to KPro implantation, had undergone Ahmed glaucoma valve (AGV) implantation to control an elevated intraocular pressure (IOP). One day after surgery, the tube was observed to be embedded in the residual lens capsule. The capsule was opened by one 1.5 mJ laser pulse, with a subsequent drop in the IOP. In patient 2, the AGV and KPro had been implanted simultaneously. One month after surgery, the IOP increased to 35 mmHg, estimated by palpation, and a vitreous gel was seen blocking the tube. A Nd:YAG laser pulse was used to open the occluded tube. In patient 3, the tube was blocked by iris tissue; Nd:YAG laser treatment opened the tube. CONCLUSIONS: The cases described here indicate that Nd:YAG laser treatment seems to be a valuable option for opening an occluded AGV tube in patients with KPro implantation. The correct location of the tube tip, visualized through the KPro optic, is essential for laser treatment.

Boston Type I Keratoprosthesis Implantation Following Autologous Submandibular Gland Transplantation for End Stage Ocular Surface Disorders.

PURPOSE: To describe the results of Boston keratoprosthesis implantation in a patient with Stevens-Johnson syndrome following autologous submandibular gland transplantation. DESIGN: Observational case report. METHODS: We report the case of a man diagnosed with Stevens-Johnson syndrome. Autologous submandibular gland transplantation was performed in the right eye in 2008 to ameliorate tear film deficiency. Due to the improvement in the microenvironment of the ocular surface, Boston keratoprosthesis implantation was performed in the right eye in 2011. RESULTS: He maintained a VA of 20/100 for 12 months. At the last follow-up visit (54 months), his VA had declined to finger count level due to de novo glaucoma, which was treated with glaucoma drainage device implantation, cyclophotocoagulation and topical anti-glaucoma medications. CONCLUSIONS: The procedures described provide patients with end-stage ocular surface disease an option to lessen the severity of keratoconjunctivitis sicca and to regain their VA.

Boston Keratoprosthesis Outcomes in Severe Ocular Chemical Burns in Southern China: A Retrospective Study.

INTRODUCTION: The objective of this study was to report clinical outcomes (functional and anatomic) of Boston keratoprosthesis (KPro) after severe chemical burns in Southern China. METHODS: Nineteen patients (19 eyes) that sustained severe chemical injuries in Southern China were enrolled in this retrospective study in our hospital between May 2009 and June 2015. KPro implantation in these patients was performed by a single experienced surgeon (Jiaqi Chen). The parameters evaluated in this study included diagnosis, comorbidity, preoperative and postoperative visual acuity (VA), complications, KPro retention, histological and immunohistochemical results of retroprosthetic membrane (RPM) and mucous membrane over the optic cylinder. RESULTS: The mean age of the patients was 42.7 ± 11.3 years (range 29-62 years). All patients were male. Of the 19 included eyes, nine had acid burns, and 10 had alkali burns. Ten patients had previously undergone failed penetrating keratoplasty. The mean follow-up time was 41.3 ± 5.5 months (range 36-56 months). Preoperatively, the VA of the patients ranged from hand movement to light perception. Postoperatively, 17 patients (89.4%) achieved at least 20/200 once, and 7 patients (36.8%) achieved at least 20/200 and maintained this acuity until the last follow-up. The initial KPro was retained in 14 (73.6%) eyes and successfully replaced in one eye. Postoperative complications included RPM in 10 eyes, glaucoma in 6 eyes, retinal detachment in 2 eyes, corneal melting in 5 eyes, ischemic optic neuropathy in 1 eye, and overgrowth of the mucous membrane over the optical cylinder in 2 eyes. The histological and immunohistochemical results of the RPM showed granulomatous disorders and mucous membrane over the optic cylinder of conjunctival origin. CONCLUSION: KPro surgery can restore useful vision in patients suffering from severe chemical burns. However, postoperative VA declined with the development of complications, and ocular surface disorders caused by the chemical burns were associated with a greater incidence of KPro retention failure. The retention rate was comparable in patients using ipsilateral autologous corneal tissue with allograft corneal tissue. FUNDING: Science and Technology Foundation of Guangdong Province of China, Grant Number 2014A020212714.

Connexin expression patterns in diseased human corneas.

The present study aimed to explore the feasibility of using antisense connexin (Cx) treatment to promote corneal wound healing, and to investigate the changes of Cx gap junction proteins in terms of mRNA, protein expression and distribution in human corneas that were diseased due to various causes. A total of 13 diseased corneas were studied, which were obtained from five eyes injured by chemical burns, five infected eyes and three eyes with Stevens-Johnson syndrome (SJS)-affected corneas. Total RNA was extracted from the corneas and processed by qPCR with isoform primers to detect the expression of eight Cxs. Flow cytometry was adopted to determine the differences in the expression levels of Cx26, Cx31.1 and Cx43. Immunofluorescence was employed to show the localization of the three aforementioned Cxs. The qPCR results indicated that of the eight Cxs, only Cx26, Cx31.1 and Cx43 were upregulated in diseased corneas. Flow cytometry showed that all the diseased corneal tissues, with the exception of the SJS-affected corneas, showed a significantly higher percentage of cells that expressed Cx26 and Cx31.1 compared with the percentage in normal corneas (P<0.05). For Cx43, all three injured corneal groups showed a significantly higher percentage of cells that expressed Cx43 compared with the percentage in normal corneas (P<0.05). Immunohistochemical staining showed that the localization of Cx26, Cx31.1 and Cx43 differed between normal corneas and diseased corneas. This study elucidated the alteration of Cx expression patterns in several corneal diseases. The results indicated that Cx26, Cx31.1 and Cx43 are upregulated in chemically burned and infected corneas at the mRNA and protein levels, whereas only Cx43 is upregulated in SJS-affected corneas.

Surgical cooperation during implantation of a Boston type-I keratoprosthesis.

This study was designed to summarize the key points of surgical cooperation involving penetrating corneal transplantation combined with implantation of keratoprosthesis. Preoperative preparation and intraoperative procedures were fully implemented to ensure cooperation with the physicians, to observe the the severity of the disease, and to guarantee the success of the surgery.

[Preliminary study of Boston keratoprosthesis in treatment of severe late stage ocular chemical burns].

OBJECTIVE: To evaluate preliminary clinical outcome of Boston type I keratoprosthesis in ocular chemical burn patients. METHODS: Six keratoprosthesis were implanted into 6 patients of bilateral blindness. Visual acuity in these patients before the operation was light perception and all of them were unsuitable for standard penetrating corneal transplantation. The causes for corneal opacity were alkali burn in 2, sulfate acid burn in 3 and ethanol injury in 1 patient. Shirmer's test revealed severe dry eye in 3 patients, only one eye had normal lacrimal secretion. All patients were male, with follow-up period ranged from 17 to 26 months (mean 24 months). RESULTS: The postoperative visual acuity ranged from 0.05 to 0.5, 5 of them was better than 0.1. The retention rate within the follow-up period was 100%. Intraocular pressure was in normal limit, no retinal detachment was detected by type B ultrasonic examination. Postoperatively, retro-keratoprosthestic membrane occurred in 2 cases and was treated with YAG laser membranectomy, one eye complicated with elevated intraocular pressure and treated with shunt implantation. CONCLUSION: The Boston type 1 keratoprosthesis is a viable option for patients with obsolete chemical burns.

Ocular safety and pharmacokinetics study of FK506 suspension eye drops after corneal transplantation.

PURPOSE: The aim of this study was to investigate the sensitization, pharmacokinetics, and absorption of FK506 after corneal transplantation. METHODS: New Zealand albino rabbits were divided into normal and corneal transplantation groups. Each group was divided into 5 subgroups--saline, blank matrix, high-dose, medium-dose, and low-dose, respectively. There were 10 rabbits in each subgroup. One drop (25 µL) of FK506 was administered topically to both eyes of the rabbits 4 times daily for 30 days. Thirty days later, 5 rabbits of each subgroup were sacrificed after the administration of the last dose. Both eyes were enucleated; the left eye was used for pathologic examination and the right eye for the determination of FK506 distribution. The other 5 rabbits in each subgroup were sacrificed 14 days after the former 5 rabbits were sacrificed, and their eyes were enucleated for pathologic examination and tissue distribution determination as the former 5 rabbits in each subgroup (the second batch). RESULTS: Fluorescein staining and local ocular reaction provided evidence that there were no significant differences between control and FK506-instilled eyes in the rabbit model at any of the tested doses. Histologic examination revealed no ocular abnormality in the rabbits instilled with any doses of FK506 eyedrop. The peak serum concentration (C(max)) of systemic absorption ranged from 4.31±0.79 ng/mL to 14.89±6.85 ng/mL. CONCLUSION: Our study suggests that up to 0.1% FK506 administered 4 times a day (q.i.d.) topically is safe for the rabbit eye. However, further safety studies are required in view of systemic adverse effects.

Tacrolimus in the treatment of ocular diseases.

Tacrolimus (FK506) has been used successfully as a systemic immunomodulator for more than 2 decades, and numerous studies have investigated its mechanisms of action. Systemic and topical tacrolimus have been investigated as treatments for ocular surface disorders that may have an immune-based inflammatory component. In these studies, tacrolimus has shown efficacy in corneal graft rejection, inflammatory conjunctival and corneal diseases, uveitis, and graft-versus-host disease. As these disorders are often refractory to other available treatments, ophthalmic or systemic tacrolimus is a welcome nontoxic adjunct or replacement to potentially toxic topical or systemic immunosuppressive therapies.

Different mechanisms of cis-9,trans-11- and trans-10,cis-12- conjugated linoleic acid affecting lipid metabolism in 3T3-L1 cells.

Conjugated linoleic acid (CLA) has been shown to reduce body fat mass in various experimental animals. It is valuable to identify its influence on enzymes involved in energy expenditure, apoptosis, fatty acid oxidation and lipolysis. We investigated isomer-specific effects of high dose, long treatment of CLA (75.4 µmol/L, 8 days) on protein and gene expression of these enzymes in cultured 3T3-L1 cells. Proteomics identified significant up- or down-regulation of 52 proteins by either CLA isomer. Protein and gene expression of uncoupling protein (UCP) 1, UCP3, perilipin and peroxisome proliferator-activated receptor (PPAR) α increased whereas UCP2 reduced for both CLA isomers. And eight-day treatment of trans-10,cis-12 CLA, but not cis-9,trans-11 CLA, significantly up-regulated protein and mRNA levels of PKA (P<.05), CPT-1 and TNF-α (P<.01). Compared to protein expression, both isomers did not significantly influence the mRNA expression of HSL, ATGL, ACO and leptin. In conclusion, high-dose, long treatment of cis-9,trans-11 CLA did not promote apoptosis, fatty acid oxidation and lipolysis in adipocytes, but may induce an increase in energy expenditure. trans-10,cis-12 CLA exhibited greater influence on lipid metabolism, stimulated adipocyte energy expenditure, apoptosis and fatty acid oxidation, but its effect on lipolysis was not obvious.

Preparation of 0.05% FK506 suspension eyedrops and its pharmacokinetics after topical ocular administration.

PURPOSE: To investigate the stability of FK506 eye suspension and its pharmacokinetics in rabbit aqueous humor, as well as its distribution in eye tissues. METHODS: Sedimentation rate, flocculation value, redispersion time, rheological study, and accelerated experiment were determined for evaluating the stability of FK506 suspension. In a single-dose pharmacokinetic study, six rabbits were instilled a 25-microL drop of 0.05% FK506 suspension and aqueous humor samples were collected at different intervals after administration. In a multiple-dose pharmacokinetic study, a 25-microL drop of FK506 suspension was instilled into the right eye of six rabbits four times a day for 7 days. On the eighth day, aqueous humor samples were collected before the administration of the first, second, third dose, and at different checkpoints after the third dose. For tissue distribution study, six eyes per time points (18 rabbits in total) were treated with single dose of FK506 suspension, and the eyes were enucleated at 60, 100, and 240 min after treatment, then eye tissues were collected. The concentrations of FK506 in all samples were determined by LC-MS/MS. RESULTS: The preliminary results indicated that the stability of FK506 suspension was in accord with the standards of Chinese pharmacopoeia. The maximum concentrations of aqueous humor after single dose and multiple dose administrations were 31.40 +/- 9.32 ng/mL and 37.73 +/- 11.25 ng/mL, respectively. The concentration of FK506 in cornea at 60, 100, and 240 min after a single dose were 402.0 +/- 96.8 ng/g, 363.8 +/- 84.5 ng/g, and 220 +/- 62.3 ng/g, respectively. Determination of pharmacokinetic parameters of single-dose and multiple-dose administration, as well as the FK506 concentrations in eye tissues, showed that the FK506 formulation and the dosing regimen ensured the therapeutic concentration of FK506 for treating corneal allograft rejection. CONCLUSIONS: Based on the stability, single-dose and multiple-dose pharmacokinetics, and tissue distribution, FK506 suspension eyedrops may be a suitable candidate for clinical application in ophthalmology.

Conjugated linoleic acid supplementation enhances antihypertensive effect of ramipril in Chinese patients with obesity-related hypertension.

BACKGROUND: Conjugated linoleic acid (CLA) refers to a group of positional and geometrical conjugated dienoic isomers of linoleic acid. Our aim was to investigate the effect of 8-week dietary CLA supplementation on blood pressure, concentrations of plasma adiponecin, leptin, and as well as angiotensin-converting enzyme (ACE) activity in obese hypertensive subjects. METHODS: Eighty obese individuals with stage 1 uncontrolled essential hypertension were randomized in a double-blind, placebo-controlled trial. Participants were randomized to a daily dose of 4.5 g/day CLA (nine 0.5-g capsules; a 50:50 isomer blend of c 9,t 11 and t 10,c 12 CLA) with 37.5 mg/day ramipril (group 1) or placebo with 37.5 mg/day ramipril (group 2) for 8 weeks. Baseline and endpoint systolic BP, diastolic BP, and concentrations of plasma adiponecin, leptin, angiotensinogen, and ACE activity were measured. RESULTS: Treatment with CLA significantly enhanced the reduction effect of ramipril on systolic BP and diastolic BP (P < 0.05). It also increased plasma adiponectin concentration (P < 0.05) and decreased plasma concentrations of leptin and angiotensinogen (P < 0.05); however, significant change was not observed in ACE activity. CONCLUSIONS: An 8-week long supplementation of CLA enhanced the effect of ramipril on blood pressure reduction in treated obese hypertensive patients. The antihypertensive effect of CLA might be related to the changed secretion of hypertensive adipocytokines in plasma.

Determination of tacrolimus in rabbit aqueous humor by liquid chromatography-electrospray ionization tandem mass spectrometry.

A simple, sensitive and selective liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of tacrolimus (FK506) in rabbit aqueous humor. After a simple protein-precipitation by methanol, the post-treatment samples were separated on a reversed-phase, Thermo-Hypersil-BDS-C18 column with a mobile phase of a mixture of 0.1% formic acid in water, methanol and acetonitrile (5:85:10, v/v/v). Tacrolimus and ritonavir (internal standard, IS) were all detected by the selected reaction-monitoring (SRM) mode. The method developed was validated in rabbit aqueous humor with a daily working range of 0.5-100 ng/ml with correlation coefficient, r>0.99 and a sensitivity of 0.5 ng/ml as lower limit of quantification, respectively. This method was fully validated for the accuracy, precision, possible matrix effect and stability. The method proved to be accurate and specific, and was applied to the pharmacokinetic study of tacrolimus in rabbit aqueous humor.