Glaucoma Agreement in New Zealand (GAINZ).

CLINICAL RELEVANCE: With an ageing population, ophthalmologists are becoming burdened with glaucoma management, and patient care can be delayed. Therefore, the use of optometrists in glaucoma management can help alleviate the burden. BACKGROUND: The ageing population and subsequent rise of glaucoma prevalence are putting a strain on the public health system in New Zealand. Glaucoma collaborative care between optometrists and ophthalmologists has been gaining support with the aim to reduce this burden on ophthalmologists. There has been little investigation of the agreement in care and management of mild-to-moderate severity glaucoma patients by optometrists and ophthalmologists. METHODS: One hundred and three glaucomatous eyes were used in a survey where clinical history and examination, intraocular pressures (IOPs), visual field testing and optical coherence tomography (OCT) imaging were evaluated for glaucoma progression and decision-making regarding subsequent management by four participants. Two participants were glaucoma-credentialled optometrists (Group 1), and the other two were glaucoma specialists (Group 2). RESULTS: With respect to glaucoma progression, Spearman coefficients identified strong agreement between the two groups for IOP, visual fields and overall status and moderate agreement for OCT imaging. A confusion matrix was used to analyse management and found 80% ± 10% agreement between the two groups. Review periods gave an agreement of 55% ± 20% between the two groups. CONCLUSION: There was strong agreement in the assessment of glaucoma progression between the two groups. The 80% level of agreement for subsequent management between the two groups is comparable to other published reports. These results provide some reassurance that a collaborative care system can perform safely and as intended.

MicroCycle: An Integrated and Automated Platform to Accelerate Drug Discovery.

We herein describe the development and application of a modular technology platform which incorporates recent advances in plate-based microscale chemistry, automated purification, in situ quantification, and robotic liquid handling to enable rapid access to high-quality chemical matter already formatted for assays. In using microscale chemistry and thus consuming minimal chemical matter, the platform is not only efficient but also follows green chemistry principles. By reorienting existing high-throughput assay technology, the platform can generate a full package of relevant data on each set of compounds in every learning cycle. The multiparameter exploration of chemical and property space is hereby driven by active learning models. The enhanced compound optimization process is generating knowledge for drug discovery projects in a time frame never before possible.

High-throughput synthesis provides data for predicting molecular properties and reaction success.

The generation of attractive scaffolds for drug discovery efforts requires the expeditious synthesis of diverse analogues from readily available building blocks. This endeavor necessitates a trade-off between diversity and ease of access and is further complicated by uncertainty about the synthesizability and pharmacokinetic properties of the resulting compounds. Here, we document a platform that leverages photocatalytic N-heterocycle synthesis, high-throughput experimentation, automated purification, and physicochemical assays on 1152 discrete reactions. Together, the data generated allow rational predictions of the synthesizability of stereochemically diverse C-substituted N-saturated heterocycles with deep learning and reveal unexpected trends on the relationship between structure and properties. This study exemplifies how organic chemists can exploit state-of-the-art technologies to markedly increase throughput and confidence in the preparation of drug-like molecules.

Early Results of Irrigating Goniectomy With TrabEx+: A Novel Device for the Treatment of Open-angle Glaucoma.

PRCIS: Irrigating goniectomy with the TrabEx+ device can lower intraocular pressure (IOP) in patients with glaucoma, as a standalone procedure or combined with cataract surgery. PURPOSE: The aim was to describe the efficacy and safety of irrigating goniectomy performed using the TrabEx+ device, either as a standalone procedure or combined with cataract surgery, in eyes with medically treated open-angle glaucoma. METHODS: A retrospective case series of eyes treated by a single surgeon at a single UK teaching hospital. Data was collected at follow-up visits at 1 week, 3, 6, 12, 18, and 24 months postoperatively. Primary outcomes included IOP and glaucoma medication reduction after surgery. Proportion of eyes achieving >20% IOP reduction, IOP <21 mm Hg, and no reoperation were classified as surgical success. RESULTS: Seventy-three consecutive eyes of 64 patients (mean age 68.4±13.7 y) were enrolled. 62% were treated as combined procedures with cataract surgery. Overall, mean IOP decreased from 31.3±7.3 to 20.9±10.4 mm Hg at the latest follow-up (34% reduction) (P<0.001) at the latest follow-up (16.1±10.3 mo) with mean preoperative medications decreased from 2.9±1.2 to 1.9±1.3 (P<0.001). 73% met the definition of success at latest follow-up. Postoperative complications were recorded including hyphaema (17%), uveitis (3%), hypotony (1%), and persistent vitreous hemorrhage (1%). Eighteen percent required reoperation because of treatment failure. CONCLUSION: TrabEx+ appears to be effective in lowering IOP and medication with or without cataract surgery. However, long-term safety and efficacy will be better understood in a prospective study with longer follow-up.

Primary photodynamic therapy for small amelanotic choroidal melanomas: consecutive case series of 69 patients with at least 24-month follow-up.

AIMS: To investigate the success and recurrence rates and visual outcomes in a large case series of amelanotic posterior choroidal melanomas treated by means of primary photodynamic therapy (PDT) with verteporfin. METHODS: Retrospective case series from a single specialist ocular oncology centre. All patients had a clinical diagnosis of choroidal melanoma and were selected for PDT based on tumour characteristics. Included patients had at least 24 months of follow-up from initiation of treatment and all but one had not received treatment prior to PDT. RESULTS: 69 patients were included. Mean tumour thickness was 1.9 mm (range 0.5-4.4), while the mean basal diameter was 6.9 mm (range 2.4-11.0). Included lesions were stage cT1a (n=66) or cT2a (n=3). The mean duration of follow-up from treatment initiation was 57 months (range 24-116 months). Seven lesions (10%) failed to respond to PDT. 10 patients (16%) experienced recurrence during follow-up. Overall success rate in this series was 75% (n=52). 83% of successfully treated patients (n=43) maintained or gained vision by final follow-up. Visual outcomes were significantly better in those patients who received PDT therapy alone in comparison to those who needed other treatments for their melanoma (Fisher's exact test, p=0.004). Unfortunately, one patient (1.4%) in the series developed systemic metastases and died. CONCLUSION: Selected amelanotic posterior uveal melanomas may be successfully treated with PDT with retention of good vision in the majority of cases, maintained with a mean of 57 months (minimum of 24 months) of follow-up.

Blue Laser Induced Retinal Injury in a Commercial Pilot at 1300 ft.

BACKGROUND: We report what may be the first evidence-based report of a retinal laser injury to a pilot during commercial flight from a laser device on the ground. Given the significant subjective (blind spot) and objective evidence of focal retinal damage, coupled with the distance involved, we suspect the laser had a radiant power of several watts, known to be injurious to the human retina. CASE REPORT: An airline pilot presented to our department complaining of a blind spot in the upper left area of his visual field in the right eye (right supero-nasal scotoma) following exposure to a laser beam while performing a landing maneuver of a commercial aircraft. At around 1300 ft (396 m), a blue laser beam from the ground directly entered his right eye, with immediate flash blindness and pain. Spectral domain ocular coherence tomography highlighted a localized area of photoreceptor disruption corresponding to a well demarcated area of hypofluorescence on fundus autofluorescence, representing a focal outer retinal laser injury. Fundus examination a fortnight later revealed a clinically identifiable lesion in the pilot's right eye commensurate with a retinal-laser burn. DISCUSSION: The case reports highlights the growing threat to the ocular health of airline crew and, potentially, passenger safety due to the lack of regulatory oversight of high powered laser devices obtained from the internet. We strongly believe high powered handheld laser devices should not be in the possession of the general public.

What is modulating solubility in simulated intestinal fluids?

The aim of this study was to understand which parameters are responsible for the selective modulation of compounds solubility in simulated intestinal fluids. The solubility of 25 chemically diverse reference compounds was measured in simulated intestinal fluid (FaSSIF-V2) and in aqueous phosphate and maleate buffers. Electrostatic interactions between compounds and the bio-relevant medium components seem to explain the different solubility behavior observed for acids and bases. The solubility of ionized acids is not increased in FaSSIF-V2 probably due to electrostatic repulsions with the media components. Lipophilicity plays an important role but mainly for charged bases with a logP>4 (or logD(6.5)>1.9). When the aqueous solubility is mainly driven by lipophilicity, the FaSSIF-V2 components seem to improve the solubility of basic compounds to a greater extent than for compounds whose solubility is limited by crystal packing. These results suggest that ionization, lipophilicity and crystal packing play important but peculiar roles in controlling solubility in FaSSIF-V2 compared to that in aqueous buffer and this information could be useful to guide medicinal chemists and formulation scientists.