Topical ivermectin 1.0% cream in the treatment of ocular demodicosis.

PURPOSE: Ocular demodicosis can cause debilitating ocular surface disease. As ivermectin is effective at reducing Demodex proliferation in rosacea, this study investigated the efficacy of topical ivermectin 1.0% cream in treating ocular demodicosis. METHODS: This retrospective single-centre clinical practice chart analysis involved the off-label treatment of patients who had ocular demodicosis with topical ivermectin 1.0 % cream (Soolantra, Galderma Ltd, UK) applied nightly to the lid margins of both eyes for 3 months. Ocular surface health was assessed at baseline when the treatment was prescribed and followed up at 3 and 12 months after baseline. Slit lamp biomicroscopy was used to take digital images of the upper eyelid lashes. Manual image analysis with ImageJ was conducted by a masked assessor to quantify signs of ocular demodicosis including the number of lashes with collarettes, with visible Demodex tails and with follicle pouting. RESULTS: Data from a total of 75 patients with ocular demodicosis were analysed for this study (mean age 66.6 ± 13.9 years, 44 female). The numbers of lashes with collarettes (Median [Interquartile range]: 8 [4-13] at baseline to 0 [0-2] at the final visit, p < 0.001) and lashes with follicle pouting (3 [1-5] at baseline to 0 [0-1.8] at the final visit, p < 0.001) decreased with treatment. Any sign of lashes with visible tails was eliminated by the final visit (p < 0.007). Fluorescein staining severity score also improved, particularly from baseline (1 [0-2]) to the second visit (0 [0-1], p < 0.001). CONCLUSIONS: The findings of this study show evidence for the efficacy of a 3-month course of topical ivermectin 1.0% cream in treating ocular demodicosis as indicated by reduction in collarettes, follicle pouting and visible Demodex tails. More research is warranted to improve the diagnosis, management and monitoring of this condition which is often overlooked or misdiagnosed.

Tear film substance P in patients treated with neurotoxic chemotherapy.

Neurotoxic chemotherapy has been shown to be associated with reduced corneal nerves and ocular surface discomfort. Substance P is a neuropeptide expressed by sensory nerves including those in the densely innervated cornea. It is involved in both pain signaling and the regulation of epithelial and neural health. While its levels in tear fluids have been used as a neuropathic biomarker in diabetes, investigations of tear concentrations of substance P in chemotherapy-induced peripheral neuropathy have not been explored. The current cross-sectional study assessed substance P expression in tears of patients following neurotoxic chemotherapy treatment. Patients treated with paclitaxel (n = 35) or oxaliplatin (n = 30) 3-24 months prior to assessment were recruited along with healthy controls (n = 25). Flush tear collection, in-vivo corneal confocal microscopy and neurotoxicity assessments were also conducted. Enzyme-linked immunosorbent assays were used to measure substance P concentrations in collected tears, while total protein content (TPC) was measured with the bicinchoninic acid method (BCA). General linear models were used for statistical analysis. Substance P concentration was reduced in paclitaxel-treated patients [Median (Interquartile range, IQR): 1.11 (0.20-2.24) ng/ml)] compared to the oxaliplatin group [4.28 (1.01-10.73) ng/ml, p = 0.02]. Substance P expressed as a proportion of TPC was also lower in the paclitaxel group [0.00006 (0.00001-0.00010) %] compared to the oxaliplatin group [0.00018 (0.00008-0.00040) %, p = 0.005]. Substance P concentration and its percentage in TPC were also reduced in the paclitaxel group when compared to healthy controls [4.61 (1.35-18.51) ng/ml, p = 0.02; 0.00020 (0.00006-0.00060) %, p = 0.04, respectively]. Higher cumulative dose of paclitaxel was correlated with a reduction in substance P concentrations (r = -0.40, p = 0.037), however no associations were found with corneal nerve parameters or neuropathy severity (p > 0.05). While these findings show evidence for the dysregulation of tear film substance P following paclitaxel treatment, longitudinal studies should be conducted to investigate how substance P levels in tears change during treatment.

Current and Emerging Pharmacotherapeutic Interventions for the Treatment of Peripheral Nerve Disorders.

Peripheral nerve disorders are caused by a range of different aetiologies. The range of causes include metabolic conditions such as diabetes, obesity and chronic kidney disease. Diabetic neuropathy may be associated with severe weakness and the loss of sensation, leading to gangrene and amputation in advanced cases. Recent studies have indicated a high prevalence of neuropathy in patients with chronic kidney disease, also known as uraemic neuropathy. Immune-mediated neuropathies including Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy may cause significant physical disability. As survival rates continue to improve in cancer, the prevalence of treatment complications, such as chemotherapy-induced peripheral neuropathy, has also increased in treated patients and survivors. Notably, peripheral neuropathy associated with these conditions may be chronic and long-lasting, drastically affecting the quality of life of affected individuals, and leading to a large socioeconomic burden. This review article explores some of the major emerging clinical and experimental therapeutic agents that have been investigated for the treatment of peripheral neuropathy due to metabolic, toxic and immune aetiologies.

Corneal dendritic cells and the subbasal nerve plexus following neurotoxic treatment with oxaliplatin or paclitaxel.

Immune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. However, our understanding of immune processes is still incomplete and current methods of observing immune cells are time consuming or invasive. Corneal dendritic cells are potent antigen-presenting cells and can be imaged with in-vivo corneal confocal microscopy. Corneal dendritic cell densities and nerve parameters in patients treated with neurotoxic chemotherapy were investigated. Patients treated for cancer with oxaliplatin (n = 39) or paclitaxel (n = 48), 3 to 24 months prior to assessment were recruited along with 40 healthy controls. Immature (ImDC), mature (MDC) and total dendritic cell densities (TotalDC), and corneal nerve parameters were analyzed from in-vivo corneal confocal microscopy images. ImDC was increased in the oxaliplatin group (Median, Md = 22.7 cells/mm2) compared to healthy controls (Md = 10.1 cells/mm2, p = 0.001), but not in the paclitaxel group (Md = 10.6 cells/mm2). ImDC was also associated with higher oxaliplatin cumulative dose (r = 0.33, p = 0.04) and treatment cycles (r = 0.40, p = 0.01). There was no significant difference in MDC between the three groups (p > 0.05). Corneal nerve parameters were reduced in both oxaliplatin and paclitaxel groups compared to healthy controls (p < 0.05). There is evidence of elevation of corneal ImDC in oxaliplatin-treated patients. Further investigation is required to explore this potential link through longitudinal studies and animal or laboratory-based immunohistochemical research.

Corneal nerve changes following treatment with neurotoxic anticancer drugs.

Survival rates of cancer has improved with the development of anticancer drugs including systemic chemotherapeutic agents. However, long-lasting side effects could impact treated patients. Neurotoxic anticancer drugs are specific agents which cause chemotherapy-induced peripheral neuropathy (CIPN), a debilitating condition that severely deteriorates quality of life of cancer patients and survivors. The ocular surface is also prone to neurotoxicity but investigation into the effects of neurotoxic chemotherapy on the ocular surface has been more limited compared to other systemic etiologies such as diabetes. There is also no standardized protocol for CIPN diagnosis with an absence of a reliable, objective method of observing nerve damage structurally. As the cornea is the most densely innervated region of the body, researchers have started to focus on corneal neuropathic changes that are associated with neurotoxic chemotherapy treatment. In-vivo corneal confocal microscopy enables rapid and objective structural imaging of ocular surface microscopic structures such as corneal nerves, while esthesiometers provide means of functional assessment by examining corneal sensitivity. The current article explores the current guidelines and gaps in our knowledge of CIPN diagnosis and the potential role of in-vivo corneal confocal microscopy as a diagnostic or prognostic tool. Corneal neuropathic changes with neurotoxic anticancer drugs from animal research progressing through to human clinical studies are also discussed, with a focus on how these data inform our understanding of CIPN.

A Cross-Sectional Study of Sub-Basal Corneal Nerve Reduction Following Neurotoxic Chemotherapy.

Purpose: Sub-basal corneal nerves have been shown to change during neurotoxic chemotherapy treatment. This cross-sectional study investigated corneal nerve morphology in patients who have completed neurotoxic chemotherapy well after treatment cessation and its association with peripheral nerve function. Methods: Central corneal nerve fiber length (CNFL) and inferior whorl length (IWL), average nerve fiber length (ANFL), corneal nerve fiber density (CNFD) and corneal nerve branch density (CNBD), and nerve fiber area (CNFA) were examined using in vivo corneal confocal microscopy in patients with cancer who had completed treatment with either paclitaxel or oxaliplatin between 3 and 24 months prior to assessment in comparison with 2 separate groups of healthy controls. Neurological assessments were conducted including clinician- and patient-reported outcomes, and neurological grading scales. Results: Both paclitaxel- (n = 40) and oxaliplatin-treated (n = 30) groups had reduced IWL and ANFL compared to the respective healthy control groups (n = 15 in each group) (paclitaxel: IWL = P = 0.02, ANFL = P = 0.009; and oxaliplatin: IWL = P = 0.008, ANFL P = 0.02). CNFL and CNFD reduction were observed only in the paclitaxel-treated group compared with healthy controls (P = 0.008 and P = 0.02, respectively), whereas CNFA was reduced in the oxaliplatin-treated group (P = 0.04). IWL reduction correlated with worse fine hand dexterity in chemotherapy-treated patients (r = -0.33, P = 0.007). Conclusions: There is evidence of corneal nerve loss in patients with cancer who have been treated with paclitaxel and oxaliplatin well after treatment cessation associated with worse upper limb function. Translational Relevance: Sub-basal corneal nerve reduction is evident even after cessation of neurotoxic treatment. In vivo corneal confocal microscopy may be useful in the monitoring of nerve function in patients receiving chemotherapy.

A cross-sectional study of ocular surface discomfort and corneal nerve dysfunction after paclitaxel treatment for cancer.

Ocular surface dysfunction is common in patients receiving anti-cancer drug treatment. The effects of paclitaxel, a neurotoxic chemotherapeutic drug, on ocular surface discomfort associated with dry eye disease was investigated. Patients with cancer who had completed paclitaxel treatment between 3 and 24 months prior to assessment (n = 29) and age- and sex-matched healthy control subjects (n = 29) were recruited and assessed with the Ocular Surface Disease Index (OSDI) to measure ocular surface discomfort. In-vivo corneal confocal microscopy was used to evaluate corneal nerve parameters in the right eye. Peripheral neurotoxicity was assessed using patient-reported outcomes and clinical grading scales. The paclitaxel group had significantly worse OSDI total scores compared with controls (Median, Md = 19.3 and Md = 0, p = 0.007, respectively). Corneal nerve fiber and inferior whorl lengths were reduced in the paclitaxel group compared with controls (14.2 ± 4.0 and 14.4 ± 4.0 mm/mm2 vs. 16.4 ± 4.0 and 16.9 ± 4.9 mm/mm2, respectively, p = 0.04). When analyzed by presence of peripheral neuropathy, paclitaxel-treated patients with neuropathy showed worse OSDI total scores compared to those without peripheral neuropathy post-treatment (p = 0.001) and healthy controls (p < 0.001). More severe ocular discomfort and worse visual function was associated with greater peripheral neurotoxicity symptoms (r = 0.60, p = 0.001) and neuropathy severity (r = 0.49, p = 0.008), respectively. Patients who have been treated with paclitaxel have a higher risk of ocular surface discomfort associated with dry eye disease, particularly those with peripheral neuropathy. Future longitudinal studies should investigate the clinical impact of corneal nerve reduction in dry eye disease.

The impact of anticancer drugs on the ocular surface.

Cancer is a global health problem and is one of the leading causes of death worldwide. Pleasingly, the rate of survival has improved and continues in an upward trend mainly due to better diagnosis and treatment modalities. In particular, the development of anticancer drugs including cytotoxic chemotherapy, hormonal agents and targeted therapies have provided the most effective treatment options in combatting cancerous cells. However, the antineoplastic mechanisms of these drugs can also lead to undesirable systemic and ocular side effects resulting from cytotoxicity, inflammation and neurotoxicity. While survival rates are projected to increase with time, the number of patients presenting with these side effects that can substantially impact quality of life will also rise. The current paper reviews the ocular surface and adnexal side effects of anticancer drugs, the appropriate management and possible interactions between drugs for ocular surface pathology treatment and the anticancer drugs.