In severe and recurrent ocular allergies conventional ophthalmic drugs can reach their limits, especially in chronic forms. The first novel immunomodulators and biologicals are already in clinical ...use and could provide relief.
Based on the immunopathophysiological mechanisms of ocular allergies, possible targets for innovative treatment approaches are presented. An overview of promising new and future immunomodulators and biologicals and their modes of action is also given.
Current reviews on ocular allergies and the treatment of systemic allergic diseases were screened. Case reports on the treatment of ocular allergy using immunomodulators and biologicals were analyzed. The clinical relevance and possible applications are presented.
In chronic forms of ocular allergies, complex ocular surface inflammatory responses mediated via immunoglobulin E (IgE), mast cells, CD4-positive type 2 T‑helper cells and eosinophilic granulocytes are predominant. Cyclosporine A 0.1% eyedrops have been approved in Europe since 2018 for children aged 4 years and older with severe vernal keratoconjunctivitis (VKC). In addition, case reports present promising data on the systemic off-label use of biologicals, such as dupilumab or omalizumab, in refractory VKC or atopic keratoconjunctivitis (AKC).
A profound understanding of the immunopathophysiology of ocular allergies is necessary to detect further targets for future immunomodulators and biologicals. Currently, immunomodulatory therapy remains limited to cyclosporine A eyedrops. Other immunomodulatory agents, such as tacrolimus and biologicals can only be used off-label. Further studies on the controlled clinical use of these substances in the treatment of VKC or AKC are underway.
Proliferative vitreoretinopathy (PVR) is currently treated surgically. Reliable pharmaceutical options would be desirable, and numerous drugs have been proposed. This
study is intended to ...systematically compare and determine the most promising candidates for the treatment of PVR.
A structured literature review was conducted in the "PubMed" database to identify previously published agents proposed for medical treatment of PVR -36 substances that met the inclusion criteria. Toxicity and antiproliferative effects were evaluated on primary human retinal pigment epithelial (hRPE) using colorimetric viability assays. The seven substances with the widest therapeutic range between toxicity and no longer detectable antiproliferative effect were then validated with a bromodeoxyuridine assay and a scratch wound healing assay using primary cells derived from surgically excised human PVR membranes (hPVR).
Among 36 substances, 12 showed no effect on hRPE at all. Seventeen substances had a significant (
< 0.05) toxic effect of which nine did not have an antiproliferative effect. Fifteen substances significantly reduced hRPE proliferation (
< 0.05). The seven most promising drugs with the highest difference between toxicity and antiproliferative effects on hRPE were dasatinib, methotrexate, resveratrol, retinoic acid, simvastatin, tacrolimus, and tranilast. Whereof resveratrol, simvastatin, and tranilast additionally showed antiproliferative and dasatinib, resveratrol, and tranilast antimigratory effects on hPVR (
< 0.05).
This study presents a systematic comparison of drugs that have been proposed for PVR treatment in a human disease model. Dasatinib, resveratrol, simvastatin, and tranilast seem to be promising and are well-characterized in human use.
To determine the effect of lockdown on medical care, with the example of ophthalmology.
Patients in a period during the first lockdown were compared to a non-lockdown period, with a total of 12 259 ...patients included in an observational study. Changes in different areas (elective, emergency, inpatients, surgeries) and eye care subspecialties were compared. Emergency patients were analyzed according to severity and urgency. Patients showing hints requiring treatment for urgent cardiovascular diseases were determined. Differences in patients who would have suffered severe vision loss without treatment were identified and the QALY (quality-adjusted life years) loss was determined accordingly. A model to prioritize patient visits after the end of lockdown or in future lockdown scenarios was developed. Data were collected at the University Eye Hospital LMU Munich and patient files were reviewed individually by ophthalmologists.
The average patient number decreased by - 59.4% (p < 0.001), with a significant loss in all areas (elective, emergency, inpatients, surgeries; p < 0.001). There was a decline of - 39.6% for patients at high risk/high severity. Patients with indications of a risk factor of future stroke declined significantly (p = 0.003). QALY loss at the university eye hospital was 171, which was estimated to be 3160 - 24 143 for all of Germany. Working up high losses of outpatients during these 8 weeks of projected lockdown in Germany would take 7 - 23 weeks under normal circumstances, depending on ophthalmologist density. The prioritization model can reduce morbidity by up to 78%.
There was marked loss of emergency cases and patients with chronic diseases. Making up for the losses in examinations and treatments will theoretically take weeks to months. To reduce the risk of morbidity, we recommend a prioritization model for rescheduling and future lockdown scenarios.
Adequate visual acuity significantly contributes to the age-appropriate development of children's neurobehavior. Infantile corneal opacities are rare but implicate a high potential for amblyopia.
...This review aims to provide an overview of the most common causes of infantile corneal opacities and highlights ophthalmopathological correlations.
The following review is based on an extensive literature search.
If metabolic diseases, traumatic or infectious events can be excluded as a cause for an infantile corneal opacity, it is important to focus on the 3Ds, corneal dysgenesis, corneal dystrophy or corneal degeneration.
If corneal opacities occur in childhood, early recognition, diagnosis, and initiation of treatment, including prophylaxis of amblyopia, are of utmost importance. In unexplained corneal opacities the histopathological work-up of the explanted cornea can contribute to the final diagnosis.
To investigate the most peripheral corneal nerve plexus using high-resolution micro-optical coherence tomography (µOCT) imaging and to assess µOCT's clinical potential as a screening tool for corneal ...and systemic diseases.
An experimental high-resolution (1.5 × 1.5 × 1 µm) µOCT setup was applied for three-dimensional imaging of the subbasal nerve plexus in nonhuman primates (NHPs) and swine within 3 hours postmortem. Morphologic features of subbasal nerves in µOCT were compared to β3 tubulin-stained fluorescence confocal microscopy (FCM). Parameters such as nerve density, nerve distribution, and imaging repeatability were evaluated, using semiautomatic image analysis in form of a custom corneal surface segmentation algorithm and NeuronJ.
Swine and NHP corneas showed the species-specific nerve morphology in both imaging modalities. Most fibers showed a linear course, forming a highly parallel pattern, converging in a vortex with overall nerve densities varying between 9.51 and 24.24 mm/mm2. The repeatability of nerve density quantification of the µOCT scans as approximately 88% in multiple image recordings of the same cornea.
Compared to the current gold standard of FCM, µOCT's larger field of view of currently 1 × 1 mm increases the conclusiveness of density measurements, which, coupled with µOCT's feature of not requiring direct contact, shows promise for future clinical application. The nerve density quantification may be relevant for screening for systemic disease (e.g., peripheral neuropathy).
Technological advances in OCT technology may enable a quick assessment of corneal nerve density, which could be valuable evaluating ophthalmic and systemic peripheral innervation.
To evaluate the
feasibility of corneal stromal filler injection to create bifocality to correct presbyopia by flattening the central posterior corneal surface and thus increase refractive power.
...Femtosecond laser-assisted corneal stromal pockets of varying diameters close to the posterior corneal curvature were cut into rabbit eyes
. Subsequently, hyaluronic acid was injected to flatten the central posterior curvature. Refractive parameters were determined using perioperatively acquired three-dimensional optical coherence tomography (OCT) scans. Using micrometer-resolution OCT, corneal endothelial cell morphology and density were evaluated.
Following filler injection into the corneal stromal pockets, a fair volume-dependent increase of central refractive power up to 4 diopters (dpt) was observed. Unremarkable refractive changes of the peripheral posterior (3 mm, 0.20 ± 0.11 dpt; 2 mm, 0.11 ± 0.10 dpt) and the anterior corneal curvature (3 mm, 0.20 ± 0.34 dpt; 2 mm, 0.33 ± 0.31 dpt) occurred. Only negligible changes in astigmatism were observed. Different sizes of optical zones could be established. Furthermore, no alterations of corneal endothelial morphology or endothelial cell density (2831 ± 356 cells/mm
vs. 2734 ± 292 cells/mm
;
= 0.552) due to the adjacent laser treatment were observed.
The
investigations proved the principle of injecting a filler material into femtosecond laser-created corneal stromal pockets close to the posterior corneal curvature as an efficacious, individually adjustable, and novel approach to correct presbyopia without ablating corneal tissue.
Due to the aging population worldwide, presbyopia is an increasing problem; thus, our study may encourage further exploration to extend the treatment spectrum of clinically used femtosecond laser systems to correct presbyopia.
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