Visual restoration with KPro after face allotransplantation with a grade III phthisical eye.

The Boston Keratoprosthesis type I (KPro-I) has been shown to be successful in restoring vision after severe ocular burns; however, its long-term outcomes in phthisical eyes have rarely been reported. A monocular woman with a history of severe alkali chemical injury necessitating facial transplantation presented with a light perception left eye after a complicated course, including failed KPro-I, therapeutic penetrating keratoplasty, endophthalmitis, hypotony, total retinal detachment, and structural changes, including a shrunken 18 mm axial length and eye wall thickening. The patient underwent a combined vitrectomy with silicone oil and KPro-I implantation, resulting in her regaining ambulatory visual acuity (20/250) at 3 years' follow-up.

Artifacts in OCT Retinal Nerve Fiber Layer Imaging in Patients with Boston Keratoprosthesis Type 1.

PURPOSE: To determine the clinical utility of OCT retinal nerve fiber layer (OCT RNFL) imaging for glaucoma evaluation in patients with Boston keratoprosthesis type 1 (KPro) by investigating imaging artifacts. DESIGN: Case-control study. SUBJECTS: Patients with KPro and without KPro (controls) matched for age, gender, and glaucoma diagnosis. METHODS: The most recent Cirrus OCT RNFL scan from 1 eye was categorized as having good signal strength (SS; ≥ 6 out of 10) or poor SS (< 6). Those with good SS were analyzed by 2 independent reviewers for artifacts. Images with good SS and no artifacts affecting the scanning circle were considered useful for glaucoma evaluation. MAIN OUTCOME MEASURES: The incidence of poor SS and artifacts in OCT RNFL images; patient characteristics associated with useful scans. RESULTS: Sixty-five patients with KPro and 75 controls were included; 89.2% of KPro patients and 89.3% of control subjects had glaucoma (P = 0.98). Forty percent of KPro patients and 5.3% of controls had poor SS (P < 0.001). The proportion of images with either poor SS or artifacts was similar in KPro (76.9%) vs. controls (72.0%, P = 0.51). The most common artifacts in both groups were missing data (43.6%, 53.2%, respectively, P = 0.32) and motion artifact (25.6%, 19.7%, respectively, P = 0.47). Images were useful for glaucoma evaluation in 43.1% of KPro patients and in 69.3% of controls (P = 0.002). In the KPro group, patients with useful OCT scans, compared with those without, had better visual acuity (0.4 ± 0.3 vs. 0.9 ± 0.7 logarithm of the minimum angle of resolution, P = 0.004), and did not have congenital corneal pathologies (0.0% vs. 24.3%, P = 0.008). A multivariate analysis showed that KPro patients with older age had higher odds of useful OCT images (odds ratio, 1.05; P = 0.03). Among KPro patients with useful OCT scans, retinal nerve fiber layer thickness correlated with observed cup-to-disc ratio (Pearson correlation: r = -0.42, P = 0.03). CONCLUSIONS: The rate of OCT RNFL images with either poor signal strength or artifacts in the KPro and control population was comparable. In patients with KPro, where intraocular pressure measurements are difficult and glaucoma is highly prevalent and often severe, OCT RNFL imaging can be useful for glaucoma evaluation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effect of SPARC Suppression in Mice, Perfused Human Anterior Segments, and Trabecular Meshwork Cells.

Purpose: Secreted protein, acidic and rich in cysteine (SPARC) elevates intraocular pressure (IOP), increases certain structural extracellular matrix (ECM) proteins in the juxtacanalicular trabecular meshwork (JCT), and decreases matrix metalloproteinase (MMP) protein levels in trabecular meshwork (TM) endothelial cells. We investigated SPARC as a potential target for lowering IOP. We hypothesized that suppressing SPARC will decrease IOP, decrease structural JCT ECM proteins, and alter the levels of MMPs and/or their inhibitors. Methods: A lentivirus containing short hairpin RNA of human SPARC suppressed SPARC in mouse eyes and perfused cadaveric human anterior segments with subsequent IOP measurements. Immunohistochemistry determined structural correlates. Human TM cell cultures were treated with SPARC suppressing lentivirus. Quantitative reverse transcriptase polymerase chain reaction (PCR), immunoblotting, and zymography determined total RNA, relative protein levels, and MMP enzymatic activity, respectively. Results: Suppressing SPARC decreased IOP in mouse eyes and perfused human anterior segments by approximately 20%. Histologically, this correlated to a decrease in collagen I, IV, and VI in both the mouse TM and human JCT regions; in the mouse, fibronectin was also decreased but not in the human. In TM cells, collagen I and IV, fibronectin, MMP-2, and tissue inhibitor of MMP-1 were decreased. Messenger RNA of the aforementioned genes was not changed. Plasminogen activator inhibitor 1 (PAI-1) was upregulated in vitro by quantitative PCR and immunoblotting. MMP-1 activity was reduced in vitro by zymography. Conclusions: Suppressing SPARC decreased IOP in mice and perfused cadaveric human anterior segments corresponding to qualitative structural changes in the JCT ECM, which do not appear to be the result of transcription regulation.

Purtscher-like retinopathy following a bowel movement.

Purpose: To describe a case of Purtscher-like retinopathy that developed after a bowel movement. Observations: A 32-year-old male presented with blurry vision and bilateral temporal paracentral scotomas that developed immediately after standing up from a bowel movement. Fundoscopic examination was notable for bilateral cotton wool spots in the nasal macula. Optical coherence tomography showed bilateral intraretinal fluid, subfoveal fluid, and scattered areas of inner retinal hyperreflectivity and thickening corresponding to the areas of cotton wool spots on examination. No treatment was administered and the patient had significant improvement in symptoms 2 days later with resolution of macular edema. Conclusions: Here we report a case of Purtscher-like retinopathy after a bowel movement. Although the exact mechanism of Purtscher-like retinopathy is unknown, there are multiple reports of Purtscher-like retinopathy after extreme events involving Valsalva, such as during weightlifting, and we postulate that this presentation is likely of similar pathophysiology.

Ocular complications with the use of radium-223: a case series.

BACKGROUND: Radium-223 is used for the treatment of osseous metastases in castrate-resistant prostate cancer, and has been shown to increase time to the first skeletal-related event, reduce the rate of hospitalization, and improve quality of life. It is well tolerated, with hematologic toxicity as the main adverse event. Thus far, no ocular complication has been reported in the literature after initial administration of radium-223 with a single case reported of ocular complications after a patient's second course of radium-223. CASE PRESENTATIONS: We present three cases of ocular complications after the use of radium-223 in patients with metastatic prostatic adenocarcinoma. Ocular complications presented as blurry vision, and formal diagnosis included uveitis and hyphema. CONCLUSIONS: Documentation of adverse events is exceedingly important due to the high incidence of metastatic prostate cancer and increasing interest for the use of radium-223 in other osteoblastic disease. The authors postulate that these ocular complications may be a result of radiation's potential effect on neovascularization, polypharmacy, or the biomolecular effects of radium-223 on integral signaling proteins, potentially coupled with poor underlying ocular health.

Novel treatment of papillomatous conjunctival lesions using pattern scanning laser photocoagulation: 1-Year results.

PURPOSE: To evaluate the safety and 1-year effect of pattern scanning laser photocoagulation treatment for pedunculated papillomatous and sessile conjunctival lesions in a low-resource setting with extremely limited operating room access. METHODS: Adult patients with clinical diagnosis of conjunctival papilloma underwent complete ophthalmologic exam including anterior segment photography. After topical anesthesia and toluidine blue 1% instillation, the lesion was treated by pattern scanning photocoagulation using a duration time that varied from 20 to 100 ms and power from 600 to 1800 mW, treating the entire lesion surface with a 2 mm margin. Patients were examined weekly for a month then monthly and underwent retreatment as necessary. RESULTS: Six patients and seven eyes that had clinically significant non-malignant pedunculated or sessile papillomatous lesions were treated. All lesions responded to treatment, with complete resolution after an average of 2.3 sessions. Procedures were well tolerated with only minor mild discomfort persisting up to two days post-treatment. Patients were followed for a mean follow-up time of 13 months with no recurrences reported. CONCLUSION: Short-term results of the pattern scanning laser photocoagulation approach, with toluidine blue for papillomatous conjunctival lesions are favorable with a 100% success rate in this cohort. This rate is comparable to surgical excision. This novel strategy proved to be a less resource intensive alternative that not only could demonstrate its usefulness in settings with chronic operating room shortages, but also in recurrent cases. Longer follow-ups with a larger sample size and cost-analysis are necessary to confirm our findings.

The alternative complement pathway aids in vascular regression during the early stages of a murine model of proliferative retinopathy.

Proliferative retinopathic diseases often progress in 2 phases: initial regression of retinal vasculature (phase 1) followed by subsequent neovascularization (NV) (phase 2). The immune system has been shown to aid in vascular pruning in such retinopathies; however, little is known about the role of the alternative complement pathway in the initial vascular regression phase. Using a mouse model of oxygen-induced retinopathy (OIR), we observed that alternative complement pathway-deficient mice (Fb(-/-)) exhibited a mild decrease in vascular loss at postnatal day (P)8 compared with age- and strain-matched controls (P = 0.035). Laser capture microdissection was used to isolate the retinal blood vessels. Expression of the complement inhibitors Cd55 and Cd59 was significantly decreased in blood vessels isolated from hyperoxic retinas compared with those from normoxic control mice. Vegf expression was measured at P8 and found to be significantly lower in OIR mice than in normoxic control mice (P = 0.0048). Further examination of specific Vegf isoform expression revealed a significant decrease in Vegf120 (P = 0.00032) and Vegf188 (P = 0.0092). In conjunction with the major modulating effects of Vegf during early retinal vascular development, our data suggest a modest involvement of the alternative complement pathway in targeting vessels for regression in the initial vaso-obliteration stage of OIR.

Inhibition of the alternative complement pathway preserves photoreceptors after retinal injury.

Degeneration of photoreceptors is a primary cause of vision loss worldwide, making the underlying mechanisms surrounding photoreceptor cell death critical to developing new treatment strategies. Retinal detachment, characterized by the separation of photoreceptors from the underlying retinal pigment epithelium, is a sight-threatening event that can happen in a number of retinal diseases. The detached photoreceptors undergo apoptosis and programmed necrosis. Given that photoreceptors are nondividing cells, their loss leads to irreversible visual impairment even after successful retinal reattachment surgery. To better understand the underlying disease mechanisms, we analyzed innate immune system regulators in the vitreous of human patients with retinal detachment and correlated the results with findings in a mouse model of retinal detachment. We identified the alternative complement pathway as promoting early photoreceptor cell death during retinal detachment. Photoreceptors down-regulate membrane-bound inhibitors of complement, allowing for selective targeting by the alternative complement pathway. When photoreceptors in the detached retina were removed from the primary source of oxygen and nutrients (choroidal vascular bed), the retina became hypoxic, leading to an up-regulation of complement factor B, a key mediator of the alternative pathway. Inhibition of the alternative complement pathway in knockout mice or through pharmacological means ameliorated photoreceptor cell death during retinal detachment. Our current study begins to outline the mechanism by which the alternative complement pathway facilitates photoreceptor cell death in the damaged retina.

Engineered mutations change the structure and stability of a virus-like particle.

The single-coat protein (CP) of bacteriophage Qß self-assembles into T = 3 icosahedral virus-like particles (VLPs), of interest for a wide range of applications. These VLPs are very stable, but identification of the specific molecular determinants of this stability is lacking. To investigate these determinants along with manipulations that confer more capabilities to our VLP material, we manipulated the CP primary structure to test the importance of various putative stabilizing interactions. Optimization of a procedure to incorporate fused CP subunits allowed for good control over the average number of covalent dimers in each VLP. We confirmed that the disulfide linkages are the most important stabilizing elements for the capsid and that acidic conditions significantly enhance the resistance of VLPs to thermal degradation. Interdimer interactions were found to be less important for VLP assembly than intradimer interactions. Finally, a single point mutation in the CP resulted in a population of smaller VLPs in three distinct structural forms.