Severe vision impairment and blindness in childhood have a significant health burden on the child, family and society. This review article seeks to provide a structured framework for managing the ...apparently blind child presenting in the first year of life, starting from a comprehensive history and examination. Different investigation modalities and the increasingly important role of genetics will also be described, in addition to common causes of severe vision impairment. Crucially, a systematic approach to the blind infant is key to correct diagnoses and timely management. Incorrect diagnoses can be costly to all involved, however it is important to note that diagnoses can change with ongoing follow‐up and investigations. Furthermore, the modern age of ophthalmology requires a multi‐disciplinary approach and close collaboration with specialists including paediatricians, neurologists and geneticists, in addition to rehabilitation and low vision services, to ensure the best care for these vulnerable infants.
Selective laser trabeculoplasty (SLT) has been used in the treatment of glaucoma for just over a decade. Here, we review the current literature in terms of suggested mechanism, efficacy, method of ...treatment, predictors of success, adverse events, repeatability, and cost of SLT. The exact mechanism by which SLT lowers intraocular pressure (IOP) remains unknown although circumstantial evidence has come in many forms in relation to structural alteration; oxidative stress and inflammatory responses; tight junction integrity; proliferative responses; and microbubble formation. SLT is as effective as argon laser trabeculoplasty and medications in reducing IOP in glaucoma and ocular hypertension. The treatment is not uniformly effective in all eyes, and its IOP-lowering effect decreases over time. High pretreatment IOP is the strongest predictor of success; however, significant pressure reduction has also been shown in normal-tension glaucoma and in patients already taking multiple antiglaucoma drops. Mild, transient adverse effects are common. Transient IOP spikes usually resolve quickly with or without antiglaucoma treatment but may be problematic in pigmented angles. The limited available evidence suggests SLT is repeatable and cost-effective for the treatment of glaucoma and ocular hypertension.
Hemizygous pathogenic variants in
lead to defective signal transmission from retinal photoreceptors to bipolar cells and cause incomplete congenital stationary night blindness in humans. Although the ...primary defect is at the terminal end of first-order neurons (photoreceptors), there is limited knowledge of higher-order neuronal changes (inner retinal) in this disorder. This study aimed to investigate inner retinal changes in
-retinopathy by analyzing macular ganglion cell layer-inner plexiform layer (GCL-IPL) thickness and optic disc pallor in 22 subjects with molecularly confirmed
-retinopathy. Detailed ocular phenotypic data including distance and color vision, refraction and electroretinogram (ERG) were collected. Distance vision was universally reduced (mean: 0.42 LogMAR), six had abnormal color vision and myopia was common (
= 15; mean: -6.32 diopters). Mean GCL-IPL thickness was significantly lower in patients (55.00 µm) compared to age-matched controls (
= 87; 84.57 µm;
<< 0.001). The GCL-IPL thickness correlated with scotopic standard (
= 0.04) and bright-flash (
= 0.014) ERG b/a ratios and photopic b-wave amplitudes (
= 0.05). Twenty-one patients had some degree of disc pallor (bilateral in 19). Fifteen putative disease-causing, including five novel variants were identified. This study establishes macular inner retinal thinning and optic atrophy as characteristic features of
-retinopathy, which are independent of myopia and could impact potential future treatment strategies.
Occupational risk factors for interstitial lung disease (ILD) are a remediable aspect of this progressive pulmonary disorder. The association between firefighting and ILD is unknown. Our objective ...was to assess the characteristics of firefighters with ILD from a large single-center ILD registry.
The University of Chicago ILD database was reviewed for patients with a history of firefighting. Clinical information was abstracted from the medical record. The prevalence rate ratio of firefighters in the database compared to the baseline prevalence of firefighting in the Chicago metropolitan area was calculated via the Poisson distribution.
Nineteen firefighters were identified; all were men. A variety of ILD subtypes were seen across the cohort, including four patients with a diagnosis of connective tissue disease. Patients had mild forced vital capacity (FVC) and moderate diffusing capacity for carbon monoxide (DLCO) decrements on presentation; three patients died and two received lung transplantation over an average follow-up time of 76 months. Firefighters were seen at a greater proportion in the ILD registry than in the general population with a prevalence rate ratio of 3.98.
Firefighting was overrepresented in our cohort compared to the general population, suggesting that there may be a causative association between firefighting and the presence of ILD. The wide variety of ILD subtypes observed suggest that all ILD patients should be asked about their occupational history. Further investigation to identify occupational exposures and determine the benefit of remediation is needed.
Importance
Transient corneal endothelial changes are routinely noted on slit‐lamp examination immediately following selective laser trabeculoplasty (SLT).
Background
To determine the mechanism of ...transient corneal endothelial changes observed following SLT.
Design
University laboratory‐based observational study.
Samples
Ten corneas from six human cadaveric donors.
Methods
Corneas were treated with SLT, direct laser or peroxide, or used as controls. Haematoxylin and eosin staining and immunolabelling for zonula occludens‐1 (ZO‐1) and beta‐catenin were performed.
Main Outcome Measures
Histological appearance; ZO‐1 and beta‐catenin immunostaining.
Results
There were no differences in histological features between SLT‐treated and control corneas. Corneas treated with SLT or peroxide showed reduced and less regular ZO‐1 immunofluorescence along cell membranes compared with ZO‐1 expression in controls. These changes were generalized across the endothelium. There was no effect on the ZO‐1 immunostaining after direct laser. There was no difference in beta‐catenin immunostaining patterns between control, SLT and peroxide‐treated corneas.
Conclusions and Relevance
Altered ZO‐1 immunostaining may represent disassembly of tight junctions between corneal endothelial cells. The similarity of our findings between SLT‐treated and peroxide‐treated corneas suggests that both conditions trigger changes at the level of endothelial tight junctions, perhaps triggered by liberation of free radicals as previously proposed.
To determine the prevalence of choroidal abnormalities (CAs) and Lisch nodules (LNs) in children who met the clinical diagnostic criteria (CDC) alone and those with a molecularly confirmed diagnosis ...(MCD) of neurofibromatosis type 1 (NF1), and to ascertain any differences between the groups.
This was a cross-sectional observational study. All children who met the CDC and/or had MCD of NF1 and underwent eye examination were included. At least two CAs or LNs between the two eyes were set as a threshold to define the presence of either abnormality. Frequencies alongside 95% confidence intervals (CIs) were calculated. The relationship between patient age and the presence of LNs and/or CAs was estimated using logistic regression.
The study cohort included 94 patients; CAs (64%) were more prevalent than LNs (41%) (0.22; 95% CI, 0.08-0.36; P = 0.0023). The probability of the presence of LNs was lower than that of CAs across all ages (odds ratio = 0.37; 95% CI, 0.20-0.69; P = 0.00173). CAs were exclusively found in 37% of patients and LNs in 16%; 80% had either CAs or LNs, or both. In the CDC group (n = 41), the difference in prevalence (CAs = 68%, LNs = 51%) did not attain statistical significance (0.17; 95% CI, -0.06 to 0.40; P = 0.18). In the MCD group (n = 53), the difference in prevalence (CAs = 60%, LNs = 34%) was significant (0.26; 95% CI, 0.006-0.47; P = 0.023).
CAs were more frequent than LNs in pediatric NF1 patients regardless of age and MCD status. Combining ophthalmological exams with near-infrared imaging will increase the diagnostic reach in pediatric NF1.
CAs detected on near-infrared imaging are objective biomarkers in NF1. They are more prevalent and detected earlier in the pediatric population compared with LNs. Hence, the presence of CAs should be routinely ascertained in children suspected with NF1.
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•A synthetic approach to the phorboxazoles is disclosed.•An enantiospecific approach to the C1–C19 polyketide fragment is described.•A two-directional synthetic approach is described.
...A synthetic approach to the C1–C19 polyketide fragment of the phorboxazoles is disclosed here. While an initial two-directional approach was efficient, it did not proceed in a high enough yield to justify moving forward. A subsequent successful strategy for the generation of the C11–C15 pyrans of both of the phorboxazoles was achieved, and the installation of the C9 stereocenter was able to be demonstrated. Furthermore, an efficient route for the preparation of the C1–C8 fragment with suitable functionality to allow for elaboration into the complete C1–C19 fragment, with the capricious C2–C3 Z-geometry installed, was also achieved.
Aim: To report a case of metastatic small-cell neuroendocrine carcinoma presenting as an isolated choroidal mass and initially misdiagnosed as a circumscribed choroidal hemangioma. Methods: The ...clinical history, fundus findings, imaging, cytology and immunohistochemical features are described. Results: An otherwise healthy 66-year-old man was referred for a left nasal scotoma and a diagnosis of circumscribed choroidal hemangioma. Cytology showed cohesive clusters of small-to-intermediate malignant cells. The atypical cells stained positively for chromogranin, thyroid transcription factor-1 and synaptophysin consistent with small-cell neuroendocrine carcinoma. Conclusion: Small-cell neuroendocrine carcinoma metastatic to the choroid is extremely rare; however, it is particularly aggressive and should be included in the differential diagnosis of isolated choroidal lesions, even in otherwise healthy patients.
Background
Patient‐reported outcome measures (PROMs) are questionnaires that collect health outcomes directly from the people who experience them. This review critically synthesizes information on ...generic and selected condition‐specific PROMs to describe trends and contemporary issues regarding their development, validation and application.
Methods
We reviewed academic and grey literature on validated PROMs by searching databases, prominent websites, Google Scholar and Google Search. The identification of condition‐specific PROMs was limited to common conditions and those with a high burden of disease (eg cancers, cardiovascular disorders). Trends and contemporary issues in the development, validation and application of PROMs were critically evaluated.
Results
The search yielded 315 generic and condition‐specific PROMs. The largest numbers of measures were identified for generic PROMs, musculoskeletal conditions and cancers. The earliest published PROMs were in mental health‐related conditions. The number of PROMs grew substantially between 1980s and 2000s but slowed more recently. The number of publications discussing PROMs continues to increase. Issues identified include the use of computer‐adaptive testing and increasing concerns about the appropriateness of using PROMs developed and validated for specific purposes (eg research) for other reasons (eg clinical decision making).
Conclusions
The term PROM is a relatively new designation for a range of measures that have existed since at least the 1960s. Although literature on PROMs continues to expand, challenges remain in selecting reliable and valid tools that are fit‐for‐purpose from the many existing instruments.
Patient or public contribution
Consumers were not directly involved in this review; however, its outcome will be used in programmes that engage and partner with consumers.
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