Tomasz P. Stryjewski

Cost-Effectiveness of the Boston Keratoprosthesis

PURPOSE To conduct a cost-utility analysis and determine the cost-effectiveness of the Boston Keratoprosthesis (Boston Kpro). DESIGN Retrospective cohort study. METHODS setting: The Massachusetts Eye and Ear Infirmary corneal service. patients: Inclusion required a minimum 2-year follow-up. Patients with autoimmune diseases and chemical burns were excluded. Eighty-two patients were included with various indications for surgery. intervention: The keratoprosthesis is a collar button-shaped polymethylmethacrylate (PMMA) device consisting of 2 curved plates sandwiched around a corneal donor (allo)graft. The device is assembled intraoperatively and sutured to a patients eye after removing the diseased cornea. MAIN OUTCOME MEASURES Average cost-effectiveness of the keratoprosthesis was determined by cost-utility analysis, using expected-value calculations and time-tradeoff utilities. The comparative effectiveness, or gain in quality-adjusted life years (QALYs), was also sought. Cost-effectiveness was compared to recently published data on penetrating keratoplasty (PK). RESULTS A total discounted incremental QALY gain for the Boston Kpro of 0.763 correlated with a conferred QALY gain of 20.3% for the average patient. The average cost-effectiveness of the keratoprosthesis was

Retinal Detachment after Open Globe Injury

16 140 per QALY. CONCLUSIONS Comparable to corneal transplantation, with a cost-effectiveness between

Verteporfin inhibits growth of human glioma in vitro without light activation

12 000 and

Cost effectiveness of the type II Boston keratoprosthesis

16 000 per QALY, the keratoprosthesis can be considered highly cost-effective.

Genetic Correlates of Proliferative Vitreoretinopathy

PURPOSE To characterize the development of retinal detachment (RD) after open globe trauma. DESIGN Case-control study. PARTICIPANTS A total of 892 patients comprising 893 open globe injuries (OGIs), of whom 255 were ultimately diagnosed with RD, with the remaining eyes serving as controls. METHODS Retrospective chart review of patients with OGIs presenting to the Massachusetts Eye and Ear Infirmary between 1999 and 2011. Kaplan-Meier analysis was used to estimate the time to detachment, and multivariable logistic regression was used to define the clinical factors associated with RD after OGI. MAIN OUTCOME MEASURES Demographic and clinical characteristics at the time of presentation after OGI, date of RD diagnosis, and last date of follow-up. RESULTS Primary repair of the open globe was typically undertaken within hours of presentation. A total of 255 eyes were ultimately diagnosed with RD after open globe trauma, yielding an incidence of 29% (95% confidence interval, 26-32). For eyes that developed RD, 27% (69/255) detached within 24 hours of primary open globe repair, 47% (119/255) detached within 1 week, and 72% (183/255) detached within 1 month. Multivariable regression analysis revealed the presence of vitreous hemorrhage (odds ratio [OR], 7.29; P < 0.001), higher zone of injury (OR, 2.51 per integer increase in zone number; OR, 1.00-6.30; P < 0.001), and poorer logarithm of the minimum angle of resolution (logMAR) visual acuity at the time of presentation after OGI (OR, 2.41 per integer increase in logMAR visual acuity; OR, 1.00-81.30; P < 0.001) to be associated with RD. A screening tool was created: the Retinal Detachment after Open Globe Injury score. CONCLUSIONS Retinal detachment is common after open globe trauma, although often not appearing until days to weeks after the initial traumatic event. Several clinical variables at the time of initial presentation can predict the future risk of detachment.

Treatment of Refractory Acute Retinal Necrosis with Intravenous Foscarnet or Cidofovir

Verteporfin (VP), a light-activated drug used in photodynamic therapy for the treatment of choroidal neovascular membranes, has also been shown to be an effective inhibitor of malignant cells. Recently, studies have demonstrated that, even without photo-activation, VP may still inhibit certain tumor cell lines, including ovarian cancer, hepatocarcinoma and retinoblastoma, through the inhibition of the YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human glioma cell lines (LN229 and SNB19). Through western blot analysis, we identified that human glioma cells that were exposed to VP without light activation demonstrated a downregulation of YAP-TEAD-associated downstream signaling molecules, including c-myc, axl, CTGF, cyr61 and survivin and upregulation of the tumor growth inhibitor molecule p38 MAPK. In addition, we observed that expression of VEGFA and the pluripotent marker Oct-4 were also decreased. Verteporfin did not alter the Akt survival pathway or the mTor pathway but there was a modest increase in LC3-IIB, a marker of autophagosome biogenesis. This study suggests that verteporfin should be further explored as an adjuvant therapy for the treatment of glioblastoma.

SMOKING IS A RISK FACTOR FOR PROLIFERATIVE VITREORETINOPATHY AFTER TRAUMATIC RETINAL DETACHMENT

PurposeDespite demonstrated cost effectiveness, not all corneal disorders are amenable to type I Boston keratoprosthesis (KPro) implantation. This includes patients with autoimmune diseases, such as Stevens–Johnson syndrome/toxic epidermal necrolysis. Type II KPro is implanted through the eyelids in severe dry eye and cicatricial diseases, and its cost effectiveness was sought.Patients and methodsIn a retrospective chart review, 29 patients who underwent type II KPro surgery at the Massachusetts Eye and Ear Infirmary between the years 2000 and 2009 were identified. A total of 11 patients had 5-year follow-up data. Average cost effectiveness was determined by cost-utility analysis, comparing type II KPro surgery with no further intervention.ResultsUsing the current parameters, the cost utility of KPro from third-party insurer (Medicare) perspective was 63 196

Case 36: Bilateral Open Globe Injury Stemming from an Assault

/quality-adjusted life year.ConclusionEfforts to refer those less likely to benefit from traditional corneal transplantation or type I KPro, for type II KPro surgery, may decrease both patient and societal costs.

Multimodal Imaging of Elschnig Spots: A Case of Simultaneous Hypertensive Retinopathy, Choroidopathy, and Neuropathy

The experienced retinal surgeon is familiar with the frustrating task of prognosticating and preventing/treating proliferative vitreoretinopathy (PVR) after retinal detachment (RD) surgery. The imperfection of long-described clinical models for predicting PVR leaves the surgeon questioning what underlying predispositions to PVR may exist. Rojas and colleagues provide insight into this question in their candidate gene association study examining inflammatory genetic markers with the occurrence of PVR after primary RD repair. In their study, Rojas et al. identified single nucleotide polymorphisms (SNPs) in the genes SMAD7 and TNF-a between subjects who developed PVR and those who did not. SMAD7 is an intracellular signaling molecule that results in the downstream inhibition of TGF-b–mediated fibrosis. It is noteworthy that this study could not replicate the previously described TGF-b association. It is very exciting to note the TNF-a association since there are approved drugs that block this proinflammatory cytokine and have even been administered intraocularly. A major strength of this study is its design, where in the first stage, case-control samples were used to identify SNPs associated with PVR from a panel of 30 candidate genes. Then, in a second stage, the significance of these SNPs was validated in samples from multiple, independent centers. This design avoids the pitfalls of overestimation and false positives, problems common to many association studies. The authors made commendable efforts to ensure that the baseline characteristics between case and control were similar, although some differences did persist, such as the operative techniques utilized between cases and controls. These discrepancies raise the question of whether other unmeasured variables affected the outcomes of the RD surgery. Regardless of such concerns, the findings of this study are an important contribution to our understanding of the pathobiology of PVR and introduce novel possibilities for more targeted therapies of this complex and befuddling condition.

A Young Woman With Headaches and Blurry Vision

ABSTRACT Purpose: To report use of intravenous foscarnet or cidofovir for the treatment of refractory acute retinal necrosis (ARN). Methods: Retrospective chart review. Results: Four immunocompetent men aged 45–90 years presented with ARN from 2008–2014. One patient with two prior episodes of herpes simplex virus (HSV) ARN developed ARN after 6 years of antiviral prophylaxis. His condition worsened on acyclovir followed by intravenous foscarnet but responded to intravenous cidofovir (final VA in involved eye 20/20). Another patient with HSV ARN had received prolonged acyclovir prophylaxis for HSV keratitis; ARN improved after switching from acyclovir to intravenous foscarnet (final VA 20/125). Two patients with varicella zoster virus (VZV) ARN initially responded to acyclovir but developed fellow eye involvement 2–8 weeks later that worsened on acyclovir but responded to intravenous foscarnet (fellow eye final VA 20/20, 20/40). Conclusions: Cases of HSV or VZV ARN that worsen despite intravenous acyclovir treatment may respond to intravenous foscarnet or cidofovir.