Local delivery of corticosteroids in clinical ophthalmology: A review

Locally administered steroids have a long history in ophthalmology for the treatment of inflammatory conditions. Anterior segment conditions tend to be treated with topical steroids whilst posterior segment conditions generally require periocular, intravitreal or systemic administration for penetration. Over recent decades, the clinical applications of periocular steroid delivery have expanded to a wide range of conditions including macular oedema from retino‐vascular conditions. Formulations have been developed with the aim to provide practical, targeted, longer‐term and more efficacious therapy whilst minimizing side effects. Herein, we provide a comprehensive overview of the types of periocular steroid delivery, their clinical applications in ophthalmology and their side effects.     

Rational laboratory testing in uveitis: A Bayesian analysis

Uveitis encompasses a heterogeneous group of clinical entities with the common feature of intraocular inflammation. In addition to patient history and examination, a focused set of laboratory investigations is frequently necessary to establish a specific diagnosis. There is limited consensus among uveitis specialists regarding appropriate laboratory evaluation for many distinct patient presentations. The appropriateness of a laboratory test for a given case of uveitis will depend on patient-specific as well as epidemiologic factors. Bayesian analysis is a widely used framework for the interpretation of laboratory testing, but is seldom adhered to in clinical practice. Bayes theorem states that the predictive value of a particular laboratory test depends on the sensitivity and specificity of that test, as well as the prevalence of disease in the population being tested. In this review we will summarize the performance of commonly-utilized laboratory tests for uveitis, as well as the prevalence of uveitic diagnoses in different geographic practice settings. We will propose a logical framework for effective laboratory testing in uveitic disease through rigorous application of Bayesian analysis. Finally, we will demonstrate that while many highly sensitive laboratory tests offer an effective means to rule out associated systemic disease, limited test specificity and low pretest probability often preclude the diagnosis of systemic disease association with any high degree of certainty, even in the face of positive testing.     

Nitric oxide and reactive oxygen species production causes progressive damage in rats after cessation of silica inhalation.

Our laboratory has previously reported results from a rat silica inhalation study which determined that, even after silica exposure ended, pulmonary inflammation and damage progressed with subsequent fibrosis development. In the present study, the relationship between silica exposure, nitric oxide (NO) and reactive oxygen species (ROS) production, and the resultant pulmonary damage is investigated in this model. Rats were exposed to silica (15 mg/m3, 6 h/day) for either 20, 40, or 60 days. A portion of the rats from each exposure were sacrificed at 0 days postexposure, while another portion was maintained without further exposure for 36 days to examine recovery or progression. The major findings of this study are: (1) silica-exposed rat lungs were in a state of oxidative stress, the severity of which increased during the postexposure period, (2) silica-exposed rats had significant increase in lung NO production which increased in magnitude during the postexposure period, and (3) the presence of silica particle(s) in an alveolar macrophage (AM) was highly associated with inducible nitric oxide synthase (iNOS) protein. These data indicate that, even after silica exposure has ended, and despite declining silica lung burden, silica-induced pulmonary NO and ROS production increases, thus producing a more severe oxidative stress. A quantitative association between silica and expression of iNOS protein in AMs was also determined, which adds to our previous observation that iNOS and NO-mediated damage are associated anatomically with silica-induced pathological lesions. Future studies will be needed to determine whether the progressive oxidative stress, and iNOS activation and NO production, is a direct result of silica lung burden or a consequence of silica-induced biochemical mediators.     

Crossed receptive field components and crossed dendrites in cat sacrocaudal dorsal horn

The hypothesis that sacrocaudal dorsal horn neurons with crossed receptive field components on the tail have dendrites which cross to the contralateral dorsal horn was tested in a combined electrophysiological and morphological study. Dorsal horn cells in the sacrocaudal spinal cord of anesthetized cats were penetrated with horseradish peroxidase-filled microelectrodes. After mapping their low threshold mechanoreceptive fields, cells were iontophoretically injected with horseradish peroxidase. A sample of 16 well-stained cells was obtained in laminae III and IV. Cells with receptive fields crossing the dorsal midline of the tail (n - 8) had somata in the lateral ipsilateral dorsal horn, and some of these cells (5/8) had dendrites which crossed to the lateral contralateral dorsal horn. Cells with receptive fields spanning the ventral midline (n - 2) were located near the center of the fused dorsal horn, and one of these had bilateral dendrites in this region. Cells with receptive fields on the lateral tail, crossing neither the dorsal nor the ventral midline (n - 6), had cell bodies in the middle of the ipsilateral dorsal horn; half had only ipsilateral dendrites, and half had crossed dendritic branches. Although the relationship between cell receptive field (RF) location (RF center, expressed as distance from tips of toes) and mediolateral location of the cell body was statistically significant, the correlation between crossed RF components and crossed dendritic branches was not significant. © 1993 Wiley-Liss, Inc.     

Somatotopic organization of single primary afferent axon projections to cat spinal cord dorsal horn.

Horseradish peroxidase injection of identified low threshold cutaneous mechanoreceptor (LTCM) primary afferent axons was used to assess the somatotopic organization of hindlimb projections to laminae III and IV of cat dorsal horn. Multiple injections in the same animals were used to assess bilateral symmetry and precision. Thirty-one axons were injected, with more than 1 axon injected in each of 8 animals (25 axons). Somatotopic relations between their receptive field (RF) centers and the centers of their dorsal horn projections were similar to the somatotopic relations between dorsal horn cell RF centers and cell locations. Very few reversals of mediolateral somatotopic gradients (proximodistal RF location as a function of mediolateral projection center) were observed. Two afferents with nearly identical RFs in 1 animal had nearly identical projections. These observations held for many different combinations of receptor types. A simple mathematical model was used to demonstrate that assembly of dorsal horn cell RFs via passive sampling of the presynaptic neuropil by dorsal horn cell dendrites cannot account for the sizes of dorsal horn cell LTCM RFs. Hypothesized mechanisms for assembly of dorsal horn cell RFs must take into account the functional selectivity of connections required to produce RFs smaller than those predicted by the passive assembly model.     

The resolution of pituitary mass in neurosarcoidosis

Sarcoidosis is a multisystem disease that primarily affects the sinuses, lungs, skin, and eyes. In our case, a young female was referred for evaluation of post partum galactorrhea. Initial magnetic resonance imaging revealed a pituitary mass. After steroids for mild adrenal insufficiency and sinus disease, the mass had resolved on imaging. This led to further investigation and diagnosis of sarcoidosis that responded to these steroids. Only 10-15% of patients with sarcoidosis have central nervous system involvement.     

The contributions of Lavoisier, Carnot, and Mayer to understanding heat illness

Although heat illness has been described throughout recorded history, an understanding of its pathophysiology was only achieved in the 20th century. Lavoisier, Carnot, and Mayer described fundamental concepts about thermodynamics in the late 18th and early 19th centuries that were crucial to the eventual understanding of heat illness. Lavoisier recognized that the human body was a heat engine. Carnot recognized that useful heat engines must dissipate heat. Mayer recognized that humans possess the capacity to regulate body heat. The fundamental contributions of Lavoisier, Carnot, and Mayer to the understanding of heat illness have gone largely unacknowledged.