To test the hypothesis that tolerating some subretinal fluid (SRF) in patients with neovascular agerelated macular degeneration (nAMD) treated with ranibizumab using a treat-and-extend (T&E) regimen can achieve similar visual acuity (VA) outcomes as treatment aimed at resolving all SRF.Design: Multicenter, randomized, 24-month, phase 4, single-masked, noninferiority clinical trial.Participants: Participants with treatment-naïve active subfoveal choroidal neovascularization (CNV). Methods: Participants were randomized to receive ranibizumab 0.5 mg monthly until either complete resolution of SRF and intraretinal fluid (IRF; intensive arm: SRF intolerant) or resolution of all IRF only (relaxed arm: SRF tolerant except for SRF >200 mm at the foveal center) before extending treatment intervals. A 5-letter noninferiority margin was applied to the primary outcome.Main Outcome Measures: Mean change in best-corrected VA (BCVA), and central subfield thickness and number of injections from baseline to month 24.Results: Of the 349 participants randomized (intensive arm, n ¼ 174; relaxed arm, n ¼ 175), 279 (79.9%) completed the month 24. The mean change in BCVA from baseline to month 24 was 3.0 letters (standard deviation, 16.3 letters) in the intensive group and 2.6 letters (standard deviation, 16.3 letters) in the relaxed group, demonstrating noninferiority of the relaxed compared with the intensive treatment (P ¼ 0.99). Similar proportions of both groups achieved 20/40 or better VA (53.5% and 56.6%, respectively; P ¼ 0.92) and 20/200 or worse VA (8.7% and 8.1%, respectively; P ¼ 0.52). Participants in the relaxed group received fewer ranibizumab injections over 24 months (mean, 15.8 [standard deviation, 5.9]) than those in the intensive group (mean, 17 [standard deviation, 6.5]; P ¼ 0.001). Significantly more participants in the intensive group never extended beyond 4-week treatment intervals (13.5%) than in the relaxed group (2.8%; P ¼ 0.003), and significantly more participants in the relaxed group extended to and maintained 12-week treatment intervals (29.6%) than the intensive group (15.0%; P ¼ 0.005).Conclusions: Patients treated with a ranibizumab T&E protocol who tolerated some SRF achieved VA that is comparable, with fewer injections, with that achieved when treatment aimed to resolve all SRF completely.

Purpose-Microbial keratitis (MK) is a major cause of blindness in Africa. This study reports the epidemiology, causative organism, management and outcome of MK in people admitted to a large referral hospital in Northern Tanzania, and explores why the outcomes are so poor for this condition.Methods-A retrospective review of all admissions for MK during a 27-month period. Information was collected on: demographics, history, examination, microbiology, treatment and outcome.Results-170 patients with MK were identified. Presentation was often delayed (median 14 days), and more delayed if another health facility was visited first (median 21 days). Appropriate intensive antibiotic treatment was prescribed in 19% before admission. Lesions were often severe (41% >5mm). Filamentary fungi were detected in 25% of all specimens (51% of specimens with a positive result). At discharge 66% of affected eyes had a visual acuity of less than 6/60. Perforations developed in 30% and evisceration was necassary in 8%. Perforation was associated with large lesions and visiting another health facility. HIV infection was diagnosed in 16% of individuals tested, which is approximately twice the prevalence found in the wider population.Conclusions-Microbial keratitis is a significant clinical problem in this region, which generally has a very poor outcome. Delayed presentation is a critical issue. Fungal keratitis is a prominent cause and there is an indication that HIV may increase susceptibility. Prompt recognition and appropriate treatment in primary / secondary health facilities and rapid referral when needed may reduce the burden of blindness from this disease.

Summary Bivalves lay down two forms of calcium carbonate in their shells, aragonite and calcite. Shells may be wholly aragonitic, or may contain both aragonite and calcite, in separate monomineralic layers. Shells are built up of several layers of distinct aggregations of calcium carbonate crystals. These aggregations are referred to as shell structures and their general features are described. Aragonite occurs as prismatic, nacreous, crossed‐lamellar, complex crossed‐lamellar and homogeneous structures. Calcite occurs as prismatic or foliated structures. Myostracal layers (calcium carbonate laid down below sites of muscle attachment) are always aragonitic. The ligament and byssus when calcined are also invariably aragonitic. A summary of the occurrence of calcite and aragonite and the associated shell structures is given. Calcite is found only in the outer layer of superfamilies belonging to the subclass Pterio‐morphia with the exception of two species only from the Heterodont superfamily Chamacea. Generally within a superfamily shell structure and mineralogy are very constant. In all superfamilies these combinations have existed for many millions of years. It is therefore demonstrated that the prime control on shell mineralogy is genetic. Possible controls on mineralogy by the mantle cells, nature of the extrapallial fluid, nature of the periostracum and the organic matrix of the shell layers are discussed. It is known that environmental factors may modify the basic mineralogy/shell structure pattern within a superfamily. Thus there is an inverse relationship between the percentage of calcite in the shell and the mean temperature of the environment inhabited by the bivalve. A critical examination of published data shows that the evidence is convincing only in the superfamily Mytilacea. The species Mytilus californianus, which shows the greatest temperature effects, is peculiar amongst the Mytilacea in having an inner calcite layer as well as an outer one. Conflicting evidence for an inverse relationship between salinity and aragonite content is reviewed. The differences of opinion cannot be resolved without experimental work. We are grateful to the following for much useful discussion, and encouragement in many ways: Dr J. R. Baker, Dr G. E. Beedham, Dr B. C. M. Butler, Dr A. Hallam, Dr J. D. Hudson, Dr R. P. S. Jefferies, Mr J. Macrae, Dr W. S. McKerrow, Mr N. J. Morris, Mr C. P. Palmer, Mr N. Tebble, Dr E. R. Trueman and Professor A. Williams. Our best thanks are to Mr R. Cleevley for critically reviewing the manuscript. The following have rendered us considerable technical assistance: the staff of the electromicroscopy unit of the British Museum (Natural History), under the direction of Mr B. Martin; the technical staff of the Department of Geology, King's College, London and of the Department of Geology and Mineralogy, Oxford; Mrs J. M. Hall, and Mr G. Burton.

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