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Ongoing assessment of patients with Alzheimer's disease (AD) in postapproval studies is important for mapping disease progression and evaluating real-world treatment effectiveness and safety. However, interpreting outcomes in the real world is challenging owing to variation in data collected across centers and specialties and greater heterogeneity of patients compared with trial participants. Here, we share considerations for observational postapproval studies designed to collect harmonized longitudinal data from individuals with mild cognitive impairment or mild dementia stage of disease who receive therapies targeting the underlying pathological processes of AD in routine practice. This paper considers key study design parameters, including proposed aims and objectives, study populations, approaches to data collection, and measures of cognition, functional abilities, neuropsychiatric status, quality of life, health economics, safety, and drug utilization. Postapproval studies that capture these considerations will be important to provide standardized data on AD treatment effectiveness and safety in real-world settings.

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BACKGROUND/AIMS: To determine the outcomes of Boston type I keratoprosthesis implanted in elderly patients. METHODS: A retrospective case series was performed on patients at least 75 years old who received the Boston type I keratoprosthesis between 1 January 2007 and 31 December 2012. Preoperative diagnosis, interval visual acuity, keratoprosthesis retention and postoperative complications were recorded for each patient. RESULTS: Forty-four Boston type I keratoprostheses were implanted in 44 eyes of 43 patients. The most common indication for surgery was corneal graft failure (n=23; 52.3%) followed by corneal scar (n=8; 18.2%) and limbal stem cell dysfunction (n=8; 18.2%). All patients had preoperative visual acuity of ≤20/200. Thirty-six of 44 (82%) patients achieved visual acuity of 20/200 or better postoperatively, and 20 of those (55.6%) maintained 20/200 or better for 1 year after surgery. The median length of follow-up was 825 days (range: 27-2193 days), and at the last follow-up visit, 20 of 44 (45.5%) had 20/200 or better vision. The median best-corrected visual acuity (logMAR) improved from 2.6 preoperatively to 1.0 at 1 year postoperative (p<0.00001). Device retention at 1 year postoperative was 88.9%. The most common postoperative complications were retroprosthetic membrane formation in 20 patients (45.5%) and cystoid macular oedema in six patients (13.6%). One patient developed keratitis and consecutive endophthalmitis 2 months after surgery and required enucleation. CONCLUSIONS: Boston type I keratoprosthesis is an effective modality in corneal blindness in elderly patients. Failure to restore or maintain ambulatory vision was typically due to non-corneal comorbidities, often unrelated to the keratoprosthesis.

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PURPOSE: Idiopathic vitritis is a poorly understood complication after Boston keratoprosthesis surgery with unclear etiology. We sought to determine whether an association exists between periprosthetic corneal tissue loss and the development of idiopathic vitritis in keratoprosthesis recipients. METHODS: Thirteen Boston type I keratoprosthesis recipient eyes with a history of idiopathic vitritis and 34 type I keratoprosthesis recipient eyes with no history of idiopathic vitritis underwent anterior segment optical coherence tomography (AS-OCT) at a median time postoperatively of 2.4 years versus 1.9 years (range, 0.5-14.2 vs. 0.1-13.6 years), respectively. Areas of corneal graft tissue loss ("gaps") around the keratoprosthesis stem were identified and analyzed by 2 masked observers. The difference in the presence, number, and size of gaps was compared between cases and controls. RESULTS: A periprosthetic gap was identified more commonly in idiopathic vitritis cases than in controls on AS-OCT (11/13, 86% vs. 11/34, 33.3%, P < 0.001). The number of gaps between cases and controls was also significantly different (2.6 ± 1.6 vs. 0.5 ± 0.8, P < 0.001), but not the estimated gap area (0.056 ± 0.049 mm² vs. 0.039 ± 0.025 mm², P = 0.22). CONCLUSIONS: A significantly higher proportion of keratoprosthesis recipient eyes with idiopathic vitritis had corneal tissue loss around the keratoprosthesis stem than did controls. Tissue loss could serve as an entry point for debris or bacterial components, triggering idiopathic vitritis. Our study underscores the utility of AS-OCT imaging in the postoperative management of keratoprosthesis patients.

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PURPOSE: The aim of this study was to revisit the clinical paradigm attributed to Boston keratoprosthesis recipients presenting with idiopathic vitreous inflammation. METHODS: A retrospective chart review was performed of keratoprosthesis recipients at Massachusetts Eye and Ear Infirmary, from January 2000 to August 2013, for demographic data, indication(s) for surgery, timing and presentation of vitreous inflammation, and best-corrected visual acuity at baseline, on presentation, and after resolution of vitritis. RESULTS: Twenty-three (23 eyes) of 346 patients developed idiopathic vitreous inflammation after keratoprosthesis implantation. Six of 23 patients presented with signs and symptoms similar to infectious endophthalmitis but were culture negative. The proportion of patients who fit the previous paradigm of sudden painless loss of vision without external signs of infection ("sterile vitritis") at their first presentation with vitritis was only 4 of 23. Vision decline was variable (median, 9 lines on Snellen chart; range, 0-24), as was time to recovery of best vision (median, 8.9 weeks; range, 0.9-36.7). Nine eyes had repeat bouts (43 episodes in 23 patients). Ten of 43 episodes did not recover to baseline vision. Seventeen of 23 eyes with idiopathic vitritis after keratoprosthesis later developed other complications. CONCLUSIONS: The current paradigm for idiopathic vitritis after keratoprosthesis implantation includes sudden painless loss of vision with full recovery of vision on treatment with periocular corticosteroids. However, idiopathic vitritis after keratoprosthesis can also mimic infectious endophthalmitis with pain and external signs of inflammation. Visual loss can be gradual. Vision may not recover to baseline despite treatment. Vitritis may be a part of a common pathway of chronic inflammation after keratoprosthesis.

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Although some conservationists accept that not all species can be saved, we illustrate the difficulty in deciding which species are dispensable. In this article, we examine the possibility that the integrity of a forest relies on its entire faunal assemblage. In Madagascar, one faunal group, the lemurs, accounts for the greatest biomass and species richness among frugivores. For example, 7 of the 13 sympatric lemur species in Madagascar's eastern rainforests consume primarily fruit. Because of this, we suggest that some tree species may rely heavily on particular lemur taxa for both seed dispersal and germination. In Ranomafana National Park, the diets for four of the day-active lemur frugivores have been documented during annual cycles over a 5-year period. We predicted that, although the fruit of some plant taxa would be exploited by multiple lemur species, the fruit of others would be eaten by one lemur species alone. Analyses reveal that while lemurs overlap in a number of fruit taxa exploited, 46% (16/35) of families and 56% (29/52) of genera are eaten exclusively by one lemur species. We, therefore, predict local changes in forest composition and structure if certain of these lemur species are eliminated from a forest owing to hunting, disease, or habitat disturbance. We also suggest that this result may be of global significance because carbon sequestration by the tropical forests in Madagascar may be reduced as a result of this predicted change in forest composition.

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It was reported over 65 years ago that chimpanzees, like humans, vary in taste sensitivity to the bitter compound phenylthiocarbamide (PTC). This was suggested to be the result of a shared balanced polymorphism, defining the first, and now classic, example of the effects of balancing selection in great apes. In humans, variable PTC sensitivity is largely controlled by the segregation of two common alleles at the TAS2R38 locus, which encode receptor variants with different ligand affinities. Here we show that PTC taste sensitivity in chimpanzees is also controlled by two common alleles of TAS2R38; however, neither of these alleles is shared with humans. Instead, a mutation of the initiation codon results in the use of an alternative downstream start codon and production of a truncated receptor variant that fails to respond to PTC in vitro. Association testing of PTC sensitivity in a cohort of captive chimpanzees confirmed that chimpanzee TAS2R38 genotype accurately predicts taster status in vivo. Therefore, although Fisher et al.'s observations were accurate, their explanation was wrong. Humans and chimpanzees share variable taste sensitivity to bitter compounds mediated by PTC receptor variants, but the molecular basis of this variation has arisen twice, independently, in the two species.

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This study investigated the effects of habitat on the diet, population density, and social structure of a small-bodied folivore, Hapalemur griseus. Three groups of H. griseus were followed at two study sites (Tala and Vato) within Ranomafana National Park in southeastern Madagascar. These two sites differed in degree of habitat disturbance, forest composition, and forest structure, as determined by botanical plots (50 x 10 m) which were monitored twice monthly in the home ranges of three study groups (group T, n = 4; group V1, n = 4; group V2, n = 2). Tala has experienced more habitat disturbance compared to Vato, and this appeared to influence population density and group size. The H. griseus that inhabit Tala occur at much higher densities and in larger social groups than the H. griseus at Vato. These results may be attributable to: 1) a greater number of potential food sources, 2) a more dense resource base, and/or 3) higher-quality resources at Tala for this folivore. In general, dietary diversity for all groups was low, and groups exploited similar plant species. However, within this small range of food sources, each study group specialized in food sources found in the highest abundance within their home range. This resulted in dietary differences between groups within sites, as well as differences between sites. Introduced tree species such as Chinese guava (Psidium cattleyanum) may have greatly impacted the diet and social structure of those groups at Tala, whose home ranges included this food source. In contrast, Vato group 1 ingested more new and mature leaves of Ficus spp., and Vato group 2 primarily ate spider bamboo (Nastus elongatus). In conclusion, it seems that microhabitat differences, which may be related to habitat disturbance and/or other factors such as topography, influenced the food species ingested by H. griseus. Overall habitat quality, which is likely also affected by habitat disturbance, influenced general diet, population density, and group size.

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