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Subgroup by treatment interaction assessments are routinely performed when analysing clinical trials and are particularly important for phase 3 trials where the results may affect regulatory labelling. Interpretation of such interactions is particularly difficult, as on one hand the subgroup finding can be due to chance, but equally such analyses are known to have a low chance of detecting differential treatment effects across subgroup levels, so may overlook important differences in therapeutic efficacy. EMA have therefore issued draft guidance on the use of subgroup analyses in this setting. Although this guidance provided clear proposals on the importance of pre‐specification of likely subgroup effects and how to use this when interpreting trial results, it is less clear which analysis methods would be reasonable, and how to interpret apparent subgroup effects in terms of whether further evaluation or action is necessary.\ud \ud A PSI/EFSPI Working Group has therefore been investigating a focused set of analysis approaches to assess treatment effect heterogeneity across subgroups in confirmatory clinical trials that take account of the number of subgroups explored and also investigating the ability of each method to detect such subgroup heterogeneity. This evaluation has shown that the plotting of standardised effects, bias‐adjusted bootstrapping method and SIDES method all perform more favourably than traditional approaches such as investigating all subgroup‐by‐treatment interactions individually or applying a global test of interaction. Therefore, these approaches should be considered to aid interpretation and provide context for observed results from subgroup analyses conducted for phase 3 clinical trials.

PURPOSE To study sub-basal corneal nerve plexus (SCNP) parameters by in vivo corneal confocal microscopy using a new software technology and examine the effect of demographics and diabetes mellitus (DM) on corneal nerves morphology. METHODS A Confoscan 4 (Nidek Technologies) was used in this cross-sectional study to image the SCNP in 84 right eyes at the Miami Veterans Affairs eye clinic. Images were analyzed using a new semiautomated nerve analysis software program (The Corneal Nerve Analysis tool) which evaluated 9 parameters including nerve fibers length (NFL) and nerve fibers length density (NFLD). The main outcome measure was the examination of SCNP morphology by demographics, comorbidities, and HbA1c level. RESULTS Interoperator and intraoperator reproducibility were good for the 9 parameters studied (Intraclass Correlations [ICCs] 0.73-0.97). Image variability between two images within the same scan was good for all parameters (ICC 0.66-0.80). Older individuals had lower SCNP parameters with NFL and NFLD negatively correlating with age (r=-0.471, and -0.461, respectively, P

PURPOSE: The NIDEK ConfoScan4 (CS4) is a digital scanning slit confocal microscope. The corneal structure and tear film can be viewed, magnified, measured, and photographed at magnifications up to 500×, in vivo, in a noninvasive manner. The objective of this study was to evaluate and illustrate various conditions related to dry eye using the CS4 confocal microscope with the 20× noncontact lens. METHODS: The CS4 was used to evaluate the natural tear film in 58 eyes of 29 patients with normal examinations, allergic conjunctivitis, nonspecific conjunctivitis, and dry eyes. In a subset of this patient population, subjective and objective findings were used to classify mild, moderate, and severe dry eye disease states. The usefulness of confocal microscopy as an objective tool to diagnose and manage different tear film-related ocular disease was also evaluated. RESULTS: The differences in tear film composition were visible using confocal microscopy. Photographs demonstrate confocal noncontact 20× microscopy as a diagnostic tool. CONCLUSIONS: Noncontact confocal microscopy is a valuable tool in the diagnosis and treatment of dry eye syndrome and other ocular states such as allergic and nonspecific conjunctivitis. It provides a simple and effective way to observe, classify, and treat the tear film. As investigators visualize and learn more, understanding of this structure will continue to improve. [J Refract Surg. 2007;23:417-419.]

Purpose To demonstrate efficacy and safety of the implantation of neural retinal progenitor cell layers (sheets) with its retinal pigment epithelium (RPE) in retinitis pigmentosa (RP) and dry age-related macular degeneration (AMD) patients with 20/200 or worse vision in the surgery eye. Design Interventional nonrandomized clinical trial. Methods Ten patients (six RP, four AMD) received retinal implants in one eye and were followed in a phase II trial conducted in a clinical practice setting. Early Treatment Diabetic Retinopathy Study (EDTRS) was the primary outcome measure. All implant recipients and nine of 10 tissue donors were deoxyribonucleic acids typed. Results Seven patients (three RP, four AMD) showed improved EDTRS visual acuity (VA) scores. Three of these patients (one RP, two AMD) showed improvement in both eyes to the same extent. Vision in one RP patient remained the same, while vision in two RP patients decreased. One RP patient has maintained an improvement in vision from 20/800 to 20/200 ETDRS for more than five years; at the six-year examination, it was still maintained at 20/320 while the nonsurgery eye had deteriorated to hand motion vision. This patient also showed a 22.72% increase in light sensitivity at five years compared to microperimetry results at two years; the other patients showed no improved sensitivity. Although no match was found between donors and recipients, no rejection of the implanted tissue was observed clinically. Conclusions Seven (70%) of 10 patients showed improved VA. This outcome provides clinical evidence of the safety and beneficial effect of retinal implants and corroborates results in animal models of retinal degeneration.