Journal of Clinical & Translational Ophthalmology

9 pages, 252 KiB

Open AccessReview

Updates on Systemic Immunomodulation in Peripheral Ulcerative Keratitis

by Arash Maleki, Tate Valerio, Yasmin Massoudi, Maria L. Ruggeri, C. Stephen Foster and Stephen D. Anesi

J. Clin. Transl. Ophthalmol. 2024, 2(4), 131-139; https://doi.org/10.3390/jcto2040011 - 23 Oct 2024

Abstract

Peripheral ulcerative keratitis (PUK) is an inflammatory process causing thinning of the cornea, epithelial defect, and inflammatory infiltrates and is caused by several etiologies. This sight-threatening condition can indicate the presence of potentially fatal underlying systemic conditions, and, accordingly, warrants thorough investigation upon [...] Read more.

Peripheral ulcerative keratitis (PUK) is an inflammatory process causing thinning of the cornea, epithelial defect, and inflammatory infiltrates and is caused by several etiologies. This sight-threatening condition can indicate the presence of potentially fatal underlying systemic conditions, and, accordingly, warrants thorough investigation upon clinical presentation and immediate intervention in order to mitigate disease progression. This review aims to provide an update on the current diagnostic and management landscape for PUK, specifically with immunomodulatory methods in cases of noninfectious etiologies. A literature search was conducted to develop a nuanced, evidence-based perspective in which we present our preferred approaches. There are currently a number of viable options, following which a “stepladder” method is typically employed, where treatment methods are escalated as a result of inadequate clinical response to lower-level interventions. This method balances efficacy with the potential side effects of immunomodulatory medications. Ultimately, carefully monitored treatment regimens are needed to mitigate visual impairment in patients with PUK, and efforts must be made to achieve steroid-free remission to avoid the known side effects of long-term corticosteroid use. Full article

18 pages, 1216 KiB

Open AccessSystematic Review

The Current Status of OCT and OCTA Imaging for the Diagnosis of Long COVID

by Helen Jerratsch, Ansgar Beuse, Martin S. Spitzer and Carsten Grohmann

J. Clin. Transl. Ophthalmol. 2024, 2(4), 113-130; https://doi.org/10.3390/jcto2040010 - 17 Oct 2024

Abstract

(1) With persistent symptoms emerging as a possible global consequence of COVID-19, the need to understand, diagnose, and treat them is paramount. This systematic review aims to explore the potential of optical coherence tomography (OCT) and/or optical coherence tomography angiography (OCTA) in effectively [...] Read more.

(1) With persistent symptoms emerging as a possible global consequence of COVID-19, the need to understand, diagnose, and treat them is paramount. This systematic review aims to explore the potential of optical coherence tomography (OCT) and/or optical coherence tomography angiography (OCTA) in effectively diagnosing long COVID. (2) The database PubMed and, to reduce selection bias, the AI research assistant Elicit, were used to find relevant publications in the period between February 2021 and March 2024. Included publications on OCT and OCTA analysis of participants with acute COVID symptoms, those after recovery, and participants with long COVID symptoms were organized in a table. Studies with participants under the age of 18, case reports, and unrelated studies, such as pure slit-lamp examinations and subgroup analyses were excluded. (3) A total of 25 studies involving 1243 participants and 960 controls were reviewed, revealing several changes in the posterior eye. Long COVID participants displayed significant thinning in retinal layers in the OCT, including the macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL). Divergent findings in recovered cohorts featured mRNFL reduction, GCL increase and decrease, and GCL-IPL decrease. Long COVID OCTA results revealed reduced vessel density (VD) in the superficial capillary plexus (SCP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). In recovered patients, SCP consistently showed a reduction, and DCP exhibited a decrease in five out of six publications. The foveal avascular zone (FAZ) was enlarged in five out of nine publications in recovered participants. (4) During various stages of COVID-19, retinal changes were observed, but a comparison between long COVID and recovered cohorts was aggravated by diverse inclusion and exclusion criteria as well as small sample sizes. Changes in long COVID were seen in most OCT examinations as thinning or partial thinning of certain retinal layers, while in OCTA a consistently reduced vessel density was revealed. The results suggest retinal alterations after COVID that are variable in OCT and more reliably visible in OCTA. Further research with larger samples is important for advancing long COVID diagnosis and management. Full article

(This article belongs to the Topic Optical Coherence Tomography (OCT) and OCT Angiography – Recent Advances)

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14 pages, 780 KiB

Open AccessSystematic Review

Rapamycin’s Impact on Age-Related Macular Degeneration—A Systematic Review and Hormesis Perspective

by Knut Sandok Wigestrand, Santosh Gupta, Kulbhushan Sharma and Goran Petrovski

J. Clin. Transl. Ophthalmol. 2024, 2(3), 99-112; https://doi.org/10.3390/jcto2030009 - 17 Sep 2024

Abstract

Background: Pre-clinical studies related to the use of rapamycin (Sirolimus^®), a mammalian target of rapamycin (mTOR) inhibitors, for age-related macular degeneration (AMD) have shown improved therapeutic outcomes. However, knowledge of its dose–effect relationship in humans with AMD has been limited and [...] Read more.

Background: Pre-clinical studies related to the use of rapamycin (Sirolimus^®), a mammalian target of rapamycin (mTOR) inhibitors, for age-related macular degeneration (AMD) have shown improved therapeutic outcomes. However, knowledge of its dose–effect relationship in humans with AMD has been limited and requires further investigation. Objective: The aim of this study is to assess the safety and efficacy of Sirolimus^® for treatment of AMD in humans and determine the dose range for its application in the eye. Methods: A systematic literature review was conducted following the PRISMA guidelines. The MEDLINE, Embase, CINAHL, Scopus and Cochrane Central Registry of Controlled Trials databases were searched for original clinical studies examining the effects of Sirolimus^® on outcomes linked to AMD in humans. This review has been registered in the PROSPERO database. Results: Only four studies were found to satisfy the inclusion and exclusion criteria and were analyzed in this systematic review in a narrative way. The dose range of rapamycin in the limited number of studies appears to be toxic to the retina. Conclusion: Future studies should focus on establishing the optimal low-dose range of Sirolimus^® that effectively induces autophagy without causing retinal toxicity, as current data indicate a potential therapeutic window that remains underexplored. Specifically, longitudinal, controlled studies with larger, heterogeneous patient populations are necessary to determine the precise dosing that balances efficacy and safety in treating AMD. Full article

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12 pages, 1249 KiB

Open AccessArticle

Possible Correlation between Mucin Gene Expression and Symptoms of Dry Eye Syndrome Secondary to Sjogren’s Disease

by Natalie Brossard-Barbosa, Matias Agoglia, Maria Elena Vergara, Monique Costa, Ernesto Cairoli and Teresa Freire

J. Clin. Transl. Ophthalmol. 2024, 2(3), 87-98; https://doi.org/10.3390/jcto2030008 - 28 Aug 2024

Abstract

(1) Background: It is estimated that 10% of dry eye disease (DED) occurs in patients with Sjogren’s syndrome (SS-DED) and represents a challenge when it comes to treatment. Both innate and adaptive immunity participate in the pathogenesis of SS-DED. Previous studies suggest that [...] Read more.

(1) Background: It is estimated that 10% of dry eye disease (DED) occurs in patients with Sjogren’s syndrome (SS-DED) and represents a challenge when it comes to treatment. Both innate and adaptive immunity participate in the pathogenesis of SS-DED. Previous studies suggest that Th1 and Th17 cell immune responses are the main actors associated with the pathogenesis of this disease. Ocular surface mucins play a fundamental role in ocular surface homeostasis. In particular, the main transmembrane mucins, MUC1, MUC4 and MUC16, are dysregulated in DED and could be involved in the activation of pro-inflammatory cytokines at the ocular interface. Thus, the objective of this work was to analyze mucin and cytokine expression in ocular surface (OS) damage and correlate it with clinical symptoms.; (2) Methods: 18 patients with SS-DED and 15 healthy controls were included in the study. Samples of conjunctival cells were obtained through cytology impression. RNA was extracted from the collected samples and used to determine the expression of MUC1, 4 and 16 by qRT-PCR. Pro-inflammatory cytokines associated with DED pathogenesis (IL17 and IL-22) were also evaluated. The results were contrasted with the clinical findings on examination of the patients. (3) Results: We observed a significant increase in the expression of MUC1 and MUC4 in patients with SS-DED. MUC4 significantly correlated with both lower production and stability of the tear film, as well as greater superficial keratopathy. On the other hand, MUC1 and MUC16 were positively correlated with the presence of more severe DED symptoms. However, we could not reproduce an increase in IL-17 and IL-22 in DED patients as previously reported; (4) Conclusions: This work constitutes an approach to understanding how the gene expression of transmembrane mucins associates with SS-DED symptoms and clinical signs. Full article

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8 pages, 585 KiB

Open AccessOpinion

The Ocular Surface–Gut Axis in Spaceflight: Implications of Intestinal Changes in Microgravity on Tear Film Physiology

by Ritu Sampige, Joshua Ong, Ethan Waisberg, John Berdahl and Andrew G. Lee

J. Clin. Transl. Ophthalmol. 2024, 2(3), 79-86; https://doi.org/10.3390/jcto2030007 - 31 Jul 2024

Cited by 1

Abstract

With increasing space exploration, there is a rising need to evaluate the impact of spaceflight on astronauts’ health, including the effects of space-associated hazards such as microgravity. Astronauts’ reports of experienced symptoms upon spaceflight include a notable prevalence of dry eye disease (DED). [...] Read more.

With increasing space exploration, there is a rising need to evaluate the impact of spaceflight on astronauts’ health, including the effects of space-associated hazards such as microgravity. Astronauts’ reports of experienced symptoms upon spaceflight include a notable prevalence of dry eye disease (DED). Hence, there is a pressing need to understand the pathogenesis and mechanism behind space-associated DED onset, which will subsequently guide the development of necessary therapies to reduce dry eye symptoms among astronauts. One critical effect of spaceflight includes alterations to the gut microbiome. On Earth, the prior literature has established the presence of an ocular surface–gut axis and the potential role of gut dysbiosis in DED onset. Meanwhile, the literature about astronauts’ health underscores the presence of space-associated gut microbiome composition alterations and the presence of DED separately. Therefore, in this opinion article, we review and present the current literature regarding the ocular surface–gut axis on Earth and regarding potential translations to spaceflight. We present the view that, based on the existing literature, the ocular surface–gut axis may be a critical mechanism for the pathogenesis of DED in space, and this axis needs to be further explored in the context of identifying ways to reduce astronauts’ experiences of DED during spaceflight. Full article

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15 pages, 680 KiB

Open AccessReview

Hereditary Optic Neuropathies: An Updated Review

by Samuel K. Lee, Caroline Mura, Nicolas J. Abreu, Janet C. Rucker, Steven L. Galetta, Laura J. Balcer and Scott N. Grossman

J. Clin. Transl. Ophthalmol. 2024, 2(3), 64-78; https://doi.org/10.3390/jcto2030006 - 26 Jun 2024

Abstract

Hereditary optic neuropathies (HONs) are a class of genetic disorders that may lead to vision loss due to either acute or progressive injury to the optic nerve. Although HONs may commonly manifest as isolated optic atrophy, these disorders can also have a variety [...] Read more.

Hereditary optic neuropathies (HONs) are a class of genetic disorders that may lead to vision loss due to either acute or progressive injury to the optic nerve. Although HONs may commonly manifest as isolated optic atrophy, these disorders can also have a variety of characteristic clinical features and time courses that may narrow the differential diagnosis. While the two most prevalent HONs are Leber Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), the phenotypic spectrum of these conditions, as well as genetic landscape of less common optic neuropathies, have been better characterized through advances in molecular diagnostic testing. Treatment targeting various pathogenic mechanisms has been investigated, although studies of clinical applicability remain nascent. Present management largely remains supportive. In this review, we discuss the clinical features, molecular diagnosis, current treatment, and future directions for HONs. Full article

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17 pages, 916 KiB

Open AccessReview

Artificial Intelligence in Glaucoma: A New Landscape of Diagnosis and Management

by Patrick Xiang Ji, Vethushan Ramalingam, Michael Balas, Lauren Pickel and David J. Mathew

J. Clin. Transl. Ophthalmol. 2024, 2(2), 47-63; https://doi.org/10.3390/jcto2020005 - 25 May 2024

Cited by 1

Abstract

Glaucoma refers to a spectrum of progressive optic neuropathies and remains the leading cause of irreversible blindness worldwide. Its insidious onset poses serious challenges to conventional diagnostic methods and clinicians striving to detect early-stage disease for timely and effective intervention. Artificial intelligence (AI) [...] Read more.

Glaucoma refers to a spectrum of progressive optic neuropathies and remains the leading cause of irreversible blindness worldwide. Its insidious onset poses serious challenges to conventional diagnostic methods and clinicians striving to detect early-stage disease for timely and effective intervention. Artificial intelligence (AI) has demonstrated its ability to process and analyze large datasets which can help identify subtle changes in early glaucomatous clinical presentation. This study reviews the current state of AI utilization in glaucoma and elucidates the strengths and limitations of existing approaches. We dissect the role of AI in various domains: enhancing early detection and diagnosis, monitoring disease progression, and refining treatment strategies to optimize patient outcomes. Furthermore, we address the ethical, legal, and social implications, alongside the inherent limitations of AI in the clinical setting. Despite these challenges, AI holds transformative potential for glaucoma management. Future directions emphasize the need for interdisciplinary collaboration, advanced and explainable algorithm development, and equitable healthcare access to fully realize the promise of AI in combating this vision-threatening condition. Full article

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13 pages, 2331 KiB

Open AccessArticle

Mutational Analysis of the SLC4A11 Gene in a (Filipino) Family with Congenital Hereditary Endothelial Dystrophy

by Vicente Lorenzo O. Cabahug, John Paul S. Llido, Loraine Kay D. Cabral, Tricia L. Maynes, Cathlyn Leigh Pinuela, Tommee Lynne Tayengco-Tiu, Ruben Lim Bon Siong and Ma. Luisa D. Enriquez

J. Clin. Transl. Ophthalmol. 2024, 2(2), 34-46; https://doi.org/10.3390/jcto2020004 - 1 Apr 2024

Abstract

Aim: The study aims to identify if mutations in the SLC4A11 gene are present in Filipino families affected with congenital hereditary endothelial dystrophy (CHED). Methods: This is a family cohort study that investigated the genetic profile of a selected family in northern Luzon, [...] Read more.

Aim: The study aims to identify if mutations in the SLC4A11 gene are present in Filipino families affected with congenital hereditary endothelial dystrophy (CHED). Methods: This is a family cohort study that investigated the genetic profile of a selected family in northern Luzon, Philippines, whose members were diagnosed with congenital hereditary endothelial dystrophy (CHED). A patient who was diagnosed with CHED prior to this study served as the proband for this family. A detailed family history was obtained and a complete ophthalmologic examination was performed on each of the family members. A total of six affected members and three unaffected members were included in this study. DNA was isolated from peripheral blood samples of the family members, polymerase chain reaction (PCR) was used to amplify the gene’s entire coding region (19 exons and 2 putative promoter regions), and finally, the amplified regions were analyzed using DNA sequencing. Results: Consanguinity was not present in the family. Corneal haze was reported to have been present since birth or shortly thereafter in all the affected patients. Slit-lamp examination showed edematous corneas. Molecular studies of the SLC4A11 gene revealed four novel homozygous point mutations variably presenting in the six affected members, as well as the three unaffected members. One unaffected family member (I-1) had a novel sense mutation absent in the other family members. All affected siblings showed little phenotypic variability. Conclusions: This is the first report that gives us a genetic profile of a northern Luzon family with members affected by CHED. This study supports earlier findings that mutations in the SLC4A11 gene are not consistently the same among different ethnic groups worldwide, probably due to the disease’s genetic heterogeneity. Our study documented five novel mutations, adding to the growing list of mutations probably responsible for acquiring the CHED phenotype. It is possible that there are more novel mutations waiting to be discovered in this hereditary disease. Screening for these specific mutations in other families may prove useful for genetic counseling, prenatal diagnosis, and the future development of gene therapy. Full article

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8 pages, 2878 KiB

Open AccessCase Report

A Case Report of Secondary Glaucoma in a Patient with HTLV-1: Discussion about the Management of Secondary Glaucoma Due to Recurrent Granulomatous Uveitis

by Kenta Ashikaga, Teruhiko Hamanaka, Mayumi Hosogai, Takao Tanaka, Shintaro Nakao and Toshinari Funaki

J. Clin. Transl. Ophthalmol. 2024, 2(2), 26-33; https://doi.org/10.3390/jcto2020003 - 29 Mar 2024

Abstract

Purpose: to investigate secondary glaucoma resulting from uveitis in a patient infected with Human T-cell Leukemia Virus Type 1 (HTLV-1) pathologically and discuss the management of glaucoma with recurrent uveitis. Clinical course: An octogenarian woman diagnosed as a carrier of HTLV-1 experienced recurrent [...] Read more.

Purpose: to investigate secondary glaucoma resulting from uveitis in a patient infected with Human T-cell Leukemia Virus Type 1 (HTLV-1) pathologically and discuss the management of glaucoma with recurrent uveitis. Clinical course: An octogenarian woman diagnosed as a carrier of HTLV-1 experienced recurrent uveitis and a sudden rise in intraocular pressure (IOP) in both eyes. Due to the uncontrolled IOP and severely damaged visual field in her left eye, a combined procedure of trabeculectomy and DGIS (glaucoma drainage implant surgery, Baerveldt 350) was performed. The presence of HTLV-1 provirus was detected in the aqueous humor. Her trabeculectomy sample was processed for light microscopic observation. Following an irregular follow-up, she presented with a sudden decrease in vision and pain in her fellow eye, four years after the glaucoma surgeries. Her right eye exhibited a significant accumulation of mutton-fat-like keratic precipitates. Results: Clinical manifestations revealed the presence of granulomatous uveitis. The combined glaucoma surgery, along with continuous topical corticosteroid medication post-surgery in her left eye, effectively suppressed the high IOP spikes and the recurrence of uveitis for 4 years. The pathological examination of the outflow pathways showed a range of damages in Schlemm’s canal (SC), including SC endothelial loss, narrowing, and occlusion, as well as loss of trabecular meshwork (TM) cells and fused TM beams. Conclusion: Combined GDIS and trabeculectomy represents a promising approach for managing such refractory cases of secondary glaucoma. Continuous topical corticosteroid medication is strongly recommended to prevent irreversible changes in SC and TM associated with granulomatous uveitis. Full article

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11 pages, 1957 KiB

Open AccessArticle

Relationship of Visual Function with Incident Fall and Mortality among Patients with Anterior Ischemic Optic Neuropathy

by Braden V. Saba, Joshua A. Grosser, Dominic Prado, Brian A. Robusto, Javier Nahmias, Gillian Treadwell and Atalie C. Thompson

J. Clin. Transl. Ophthalmol. 2024, 2(1), 15-25; https://doi.org/10.3390/jcto2010002 - 7 Feb 2024

Abstract

The purpose of this study was to determine if worse visual acuity is associated with an increased risk of incident fall or mortality, independent of other relevant cofounders. This was a single-center retrospective cohort study of 428 new cases of anterior ischemic optic [...] Read more.

The purpose of this study was to determine if worse visual acuity is associated with an increased risk of incident fall or mortality, independent of other relevant cofounders. This was a single-center retrospective cohort study of 428 new cases of anterior ischemic optic neuropathy (AION). Separate Cox proportional hazards models were constructed to evaluate the relationship between either logMAR visual acuity (VA) or legal blindness (20/200 or worse VA) and survival time to (1) encounter for fall, (2) mortality, and (3) a composite adverse outcome. Multivariable models were adjusted for a priori confounders. In adjusted models, a 1-unit increase in logMAR VA was associated with a significantly greater risk of an incident fall (adjusted HR 1.36, 95% CI (1.06–1.73), p = 0.014) and of mortality (adjusted HR 1.44, 95% CI (1.15–1.82), p = 0.002). Meeting criteria for legal blindness was also significantly associated with a higher risk of incident fall (HR 1.80, 95% CI (1.05–3.07), p = 0.032) and mortality (adjusted HR 2.16, 95% CI (1.29–3.63), p = 0.004). Among patients with AION, worse visual acuity or legal blindness conferred a significantly increased risk of falls and mortality, independent of coexistent comorbidities. Future studies should consider fall reduction interventions for patients with poor vision from severe eye disease such as AION. Full article

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14 pages, 3495 KiB

Open AccessArticle

Preparation and In Vitro Testing of Brinzolamide-Loaded Poly Lactic-Co-Glycolic Acid (PLGA) Nanoparticles for Sustained Drug Delivery

by Ann-Marie Ako-Adounvo and Pradeep K. Karla

J. Clin. Transl. Ophthalmol. 2024, 2(1), 1-14; https://doi.org/10.3390/jcto2010001 - 9 Jan 2024

Cited by 1

Abstract

Glaucoma therapy aims at lowering intra-ocular pressure (IOP). Brinzolamide, a carbonic anhydrase inhibitor, is utilized as a second-line medication for treating ocular hypertension and primary open-angle glaucoma (POAG). The drug lowers the IOP making it a therapeutic agent against glaucoma, and due to [...] Read more.

Glaucoma therapy aims at lowering intra-ocular pressure (IOP). Brinzolamide, a carbonic anhydrase inhibitor, is utilized as a second-line medication for treating ocular hypertension and primary open-angle glaucoma (POAG). The drug lowers the IOP making it a therapeutic agent against glaucoma, and due to its poor water solubility, is commercially available as Azopt^®, a 1% ophthalmic suspension. Adverse effects such as blurred vision, ocular irritation, discomfort, and bitter taste are associated with the use of the marketed brinzolamide formulation. This study aims to test the feasibility of formulating and in vitro testing of brinzolamide-PLGA nanoparticles for improved toxicity profile. The nanoparticles were prepared by the oil-in-water (O/W) emulsion-solvent evaporation method. Particle size and zeta potential were determined by dynamic light scattering (DLS). The morphology of the nanoparticles was determined by scanning electron microscopy (SEM). Encapsulation of the drug was verified by high-performance liquid chromatography (HPLC) and the compatibility of the polymer and drug was verified by Fourier transform infrared (FTIR) spectroscopy. The in vitro drug release profile was assessed employing the dialysis method. Intracellular localization of the nanoparticles was assessed by confocal microscopy utilizing Rhodamine 123-loaded nanoparticles. Cytotoxicity of the formulation was assessed on Statens Seruminstitut Rabbit Cornea (SIRC) and transfected Human Corneal Epithelial (SV40 HCEC) cell lines. The particle size of the nanoparticle formulations ranged from 202.3 ± 2.9 nm to 483.1 ± 27.9 nm for blank nanoparticles, and 129.6 ± 1.5 nm to 350.9 ± 8.5 nm for drug-loaded nanoparticles. The polydispersity of the formulations ranged from 0.071 ± 0.032 to 0.247 ± 0.043 for blank nanoparticles, and 0.089 ± 0.028 to 0.158 ± 0.004 for drug-loaded nanoparticles. Drug loading and encapsulation efficiencies ranged from 7.42–15.84% and 38.93–74.18%, respectively. The in vitro drug release profile for the optimized formulation was biphasic, with a ~54% burst release for the initial 3 h, followed by a cumulative 85% and 99% released at 24 and 65 h, respectively. Uptake study showed nanoparticles(NPs) localization in the cytoplasm and around the nuclei of the cells. Brinzolamide-PLGA nanoparticles were successfully developed, characterized, and tested in vitro. Preliminary data show intracellular localization of the nanoparticles in the cytoplasm of SIRC and SV40 HCEC cells. The formulations appeared to be relatively non-cytotoxic to the cells. The research data from the study provided preliminary data for successful development and promising in vitro absorption efficacy for brinzolamide-loaded PLGA nanoparticle formulation. Full article

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10 pages, 1808 KiB

Open AccessArticle

Pulsed Ultrasound Modulates the Cytotoxic Effect of Cisplatin and Doxorubicin on Cultured Human Retinal Pigment Epithelium Cells (ARPE-19)

by Seyed Omid Mohammadi, Megan C. LaRocca, Christopher D. Yang, Jordan Jessen, M. Cristina Kenney and Ken Y. Lin

J. Clin. Transl. Ophthalmol. 2023, 1(4), 107-116; https://doi.org/10.3390/jcto1040013 - 27 Nov 2023

Abstract

Objective: Pulsed ultrasound has been proposed as a tool to enhance ocular drug delivery, but its effects on drug potency are not well understood. Doxorubicin-HCl and cisplatin are two drugs commonly used to treat ocular melanoma. We report the effects of pulsed ultrasound [...] Read more.

Objective: Pulsed ultrasound has been proposed as a tool to enhance ocular drug delivery, but its effects on drug potency are not well understood. Doxorubicin-HCl and cisplatin are two drugs commonly used to treat ocular melanoma. We report the effects of pulsed ultrasound on the cytotoxicity of doxorubicin-HCl and cisplatin in vitro. Methods: Cultured human retinal pigment epithelium cells (ARPE-19) were treated with doxorubicin-HCl or cisplatin in the presence or absence of ultrasound. MTT and Trypan blue assays were performed at 24 and 48 h post treatment to assess cell metabolism and death. Results: Cells treated with ultrasound plus doxorubicin-HCl demonstrated a significant decrease in metabolism compared with cells treated with doxorubicin-HCl alone. In contrast, cells treated with ultrasound plus cisplatin exhibited a significant increase in metabolism compared with cells treated with cisplatin alone for 48 h. Cells treated with cisplatin and pretreated with ultrasound (US–Cis) exhibited a significant decrease in metabolism. Cell death was similar in doxorubicin- and cisplatin-treated cells with and without ultrasound. Conclusion: Pulsed ultrasound enhances the cytotoxicity of doxorubicin-HCl at 24 and 48 h post treatment but abrogates cisplatin toxicity 48 h post treatment. This suggests ultrasound modulates cell–drug interactions in a drug-specific manner. These findings may influence the future development of ultrasound-assisted ocular drug delivery systems. Full article

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10 pages, 2078 KiB

Open AccessArticle

A Case Series of Transscleral Cyclophotocoagulation Nd:YAG Laser in Refractory Glaucoma

by Gregorio Lo Giudice, Giuseppe Miceli, Giuseppe Tumminello, Alessandro Trapani and Antonino Pioppo

J. Clin. Transl. Ophthalmol. 2023, 1(4), 97-106; https://doi.org/10.3390/jcto1040012 - 26 Oct 2023

Abstract

Purpose: To describe the efficacy and safety of surgical treatment in refractory glaucoma using transscleral cyclophotocoagulation with a diode laser (TSCPC). Cyclo-G6 laser with a G-probe delivery system (Iridex, Silicon Valley, CA, USA). Materials and Methods: 134 patients (134 eyes) with refractory glaucoma [...] Read more.

Purpose: To describe the efficacy and safety of surgical treatment in refractory glaucoma using transscleral cyclophotocoagulation with a diode laser (TSCPC). Cyclo-G6 laser with a G-probe delivery system (Iridex, Silicon Valley, CA, USA). Materials and Methods: 134 patients (134 eyes) with refractory glaucoma were included in this study. Patients received transscleral cyclophotocoagulation (TSCPC) using the IRIDEX Cyclo-G6 diode laser equipped with a G-probe delivery system. The eyes were treated with 1250–1500 mW for 3500–4000 ms depending on the iris colour. Intraocular pressure (IOP) and the count of antiglaucoma medications (AGM) were documented at the initial assessment and again at 3, 6, and 12 months following the treatment. Results: A reduction in IOP was observed in 97.73% of eyes at 12 months. At 12 months, 55.97% of the 134 eyes decreased IOP under 21 mmHg. At the 3-month mark, 96.27% of eyes attained an IOP reduction in 30% or more from their initial baseline levels, 85.61% at 6 months, and 82.17% at 12 months. A reduction in AGM was recorded for 86.07% of patients at 6 months and 87.31% at 12 months. There were no instances of severe complications reported, and minor complications were observed in 3% (4 out of 134) of the treated eyes. Conclusions: IRIDEX Cyclo-G6 laser is a surgical method effective in reducing IOP in patients with refractory glaucoma Full article

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6 pages, 498 KiB

Open AccessArticle

The Effect of Antiopioid State Laws on Prescribing Patterns in an Oculoplastic Practice

by Elahhe Afkhamnejad, Cooper Stevenson and Praveena Gupta

J. Clin. Transl. Ophthalmol. 2023, 1(3), 91-96; https://doi.org/10.3390/jcto1030011 - 18 Aug 2023

Abstract

This study aimed to find out whether three Texas state policies restricting opioid prescriptions have influenced the prescribing patterns of the oculoplastic department at the University of Texas Medical Branch (UTMB). This is a retrospective chart review of 520 patients at UTMB between [...] Read more.

This study aimed to find out whether three Texas state policies restricting opioid prescriptions have influenced the prescribing patterns of the oculoplastic department at the University of Texas Medical Branch (UTMB). This is a retrospective chart review of 520 patients at UTMB between 2019 and 2021, reporting the amount of morphine milliequivalents (MMEs) prescribed to patients undergoing one of eight oculoplastic procedures before and after passage of each state policy. Of 520 patients, 218 received opioids. There were no changes in MMEs/month after the first policy (95% CI: −0.1531–0.1256, p = 0.85), second policy (95% CI: −0.000997–0.00093, p = 0.97), or third policy (95% CI: −0.001431–0.00164, p = 0.096). The passage and implementation of three Texas state antiopioid policies were not associated with significant changes in opioid prescribing patterns following oculoplastic and orbital surgeries at UTMB. Average MMEs/month were driven by orbital-floor fractures, which composed most procedures overall. Limitations included the small population and that only a single provider was reviewed. Future studies would be beneficial in further evaluating the role of state legislation on opioid prescribing patterns and usage among patients. Full article

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12 pages, 4108 KiB

Open AccessArticle

Synergistic Effect of Substance P with Insulin and Insulin-Like Growth Factor-I on Epithelial Migration of the Transformed Human Corneal Epithelial Cells (SV-40)

by Phat Tran, Jonathan Kopel and Ted W. Reid

J. Clin. Transl. Ophthalmol. 2023, 1(3), 79-90; https://doi.org/10.3390/jcto1030010 - 17 Jul 2023

Abstract

On the cornea, daily epithelial resurfacing is a critical process to prevent the loss of normal function, ocular morbidity, corneal structure, and vision loss. There are several components to wound healing, including cellular attachment, migration, and growth. To develop a treatment for corneal [...] Read more.

On the cornea, daily epithelial resurfacing is a critical process to prevent the loss of normal function, ocular morbidity, corneal structure, and vision loss. There are several components to wound healing, including cellular attachment, migration, and growth. To develop a treatment for corneal epithelial healing, we studied the effect of substance P (SP) on corneal epithelial cell migration using a cell culture system of either transformed human corneal epithelial cells (SV-40), or rabbit corneal epithelial cells (SIRC). We investigated the effect of SP with insulin and insulin-like growth factor-I (IGF-1). We found that SP is synergistic with insulin and IGF-1 on the stimulation of transformed human corneal epithelial migration in a cell culture system, as well as in rabbit SIRC cells. The addition of either SP, insulin, or IGF-1 alone did not greatly affect epithelial migration, while the combination of SP and insulin or SP and IGF-1 markedly stimulated epithelial migration in a dose-dependent manner. The synergistic effects of SP with insulin and SP with IGF-1 were inhibited by the addition of the SP-specific inhibitor (CP96345). However, the effect of insulin and IGF-1 alone were not inhibited by the NK-1-specific inhibitor (CP96345). Our results are consistent with the need for the involvement of the neuropeptide SP in corneal epithelial wound healing of diabetic corneas where nerve-ending dropout occurs. Additionally, almost identical results were obtained with human and rabbit corneal epithelial cells. These results suggest that the maintenance of the normal integrity of the corneal epithelium might be regulated by both humoral and neural factors. Full article

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7 pages, 1402 KiB

Open AccessCase Report

Cataract Surgery following Corneal Allogenic Intrastromal Ring Segments and Implantable Collamer Lens

by Arsalan Akbar Ali, Bobby Saenz and Taj Nasser

J. Clin. Transl. Ophthalmol. 2023, 1(3), 72-78; https://doi.org/10.3390/jcto1030009 - 26 Jun 2023

Abstract

The management of cataracts in keratoconus patients poses a challenge due to the irregular corneal shape and variability in corneal topography, which may lead to errors in determining corneal power. In this report, we present a case of a 48-year-old male with a [...] Read more.

The management of cataracts in keratoconus patients poses a challenge due to the irregular corneal shape and variability in corneal topography, which may lead to errors in determining corneal power. In this report, we present a case of a 48-year-old male with a history of keratoconus and prior Visian Implantable Collamer lenses and Corneal Allogenic Intrastromal Ring Segments procedures, who presented with a nuclear cataract in his right eye. To address this patient’s complex case, he underwent ICL explantation, cataract extraction, and intraocular lens (IOL) implantation, utilizing the Johnson & Johnson Sensar AR40 monofocal 3-piece lens with a power of −9.5. The Barrett True K formula predicted a spherical equivalent of −1.76, and at the post-operative one-month follow-up, the uncorrected distance visual acuity (UDVA) was 20/60, with pinhole improvement to 20/50. The manifest refraction was −2.50–3.25 × 145, and the best corrected visual acuity was 20/25. This case report highlights the unique challenges encountered in managing keratoconus patients with a history of prior ICL and CAIRS procedures, followed by cataract extraction. Our findings underscore the importance of a comprehensive approach in the management of progressive keratoconus and cataracts to ensure optimal outcomes. Full article

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11 pages, 1602 KiB

Open AccessPerspective

Recontextualizing Neuromyelitis Optica as a Systemic Condition: A Perspective

by Parker Webber, Brianna C. Landis and Amanda E. Brooks

J. Clin. Transl. Ophthalmol. 2023, 1(2), 61-71; https://doi.org/10.3390/jcto1020008 - 24 May 2023

Abstract

Neuromyelitis optica spectrum disorder (NMOSD), a demyelinating CNS disorder in which inflammatory cells infiltrate the spinal cord and optic nerve, has been identified as an AQP4-IgG-positive disease. Some of its most common clinical characteristics are optic neuritis, acute myelitis, area postrema syndrome, and [...] Read more.

Neuromyelitis optica spectrum disorder (NMOSD), a demyelinating CNS disorder in which inflammatory cells infiltrate the spinal cord and optic nerve, has been identified as an AQP4-IgG-positive disease. Some of its most common clinical characteristics are optic neuritis, acute myelitis, area postrema syndrome, and brainstem syndrome. However, the relationship between aquaporin-4 (AQP4) and NMOSD appears to be involved in pathologies outside of the CNS due to the fact that autoimmune, muscular, and paraneoplastic syndromes are more common in patients with NMOSD. This perspective presents an analysis of the current literature on neuromyelitis optica in an effort to further understand and compile pathologies that arise outside of the CNS secondary to NMOSD. Recontextualizing neuromyelitis optica as a systemic condition will facilitate greater diagnostic ability and improved treatment approaches. Full article

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9 pages, 2966 KiB

Open AccessFeature PaperArticle

In Vitro Anti-Inflammatory Potential of Pomegranate Extract (Pomanox^®) in a Reconstituted Human Corneal Epithelium Model

by Marcos Peñalver-Mellado, Fredy Silva-Fuentes, Agustín Villar, Anna Mula and Andrea Zangara

J. Clin. Transl. Ophthalmol. 2023, 1(2), 52-60; https://doi.org/10.3390/jcto1020007 - 19 Apr 2023

Abstract

An in vitro study was conducted using a model of reconstituted human corneal epithelial (SkinEthic™ HCE/Human Corneal Epithelium) to test the modulation of cytokines secretion activity of Pomanox^® (PMX), a standardized commercial extract of pomegranate fruit characterized by high punicalagin α + [...] Read more.

An in vitro study was conducted using a model of reconstituted human corneal epithelial (SkinEthic™ HCE/Human Corneal Epithelium) to test the modulation of cytokines secretion activity of Pomanox^® (PMX), a standardized commercial extract of pomegranate fruit characterized by high punicalagin α + β content. Cell viability and inhibition of the release of interleukin-8 (IL-8) was evaluated in four conditions: negative control, positive inflammatory control with lipopolysaccharide (LPS) from Escherichia coli, positive anti-inflammatory control (LPS plus dexamethasone), and LPS plus PMX after 24 h of culture. The mean (±standard error of mean (SEM)) IL-8 level was 48.7 ± 5.1 pg/mL in the PMX condition vs. 172.7 ± 19.3 and 26.6 ± 1.2 in the LPS from E. coli and negative control, respectively (p < 0.05) and 93.8 ± 8.7 pg/mL in LPS plus dexamethasone (p = 0.165). The percentages of inhibition of IL-8 release were 45.7% for LPS plus dexamethasone and 63.8% for LPS plus PMX. The percentage of cell viability (86%) was also higher for the LPS plus PMX condition. The present findings add evidence to the anti-inflammatory effect of a PMX in an in vitro model of reconstituted corneal epithelial cells. Full article

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17 pages, 1366 KiB

Open AccessReview

The Activity of Substance P (SP) on the Corneal Epithelium

by Jonathan Kopel, Caezaan Keshvani, Kelly Mitchell and Ted Reid

J. Clin. Transl. Ophthalmol. 2023, 1(2), 35-51; https://doi.org/10.3390/jcto1020006 - 27 Mar 2023

Cited by 1

Abstract

In 1931, Von Euler and Gaddum isolated substance P (SP), an undecapeptide from the tachykinin family, from equine brain and intestine tissue extracts. Numerous types of cells, including neurons, astrocytes, microglia, epithelial, and endothelial cells, as well as immune cells including T-cells, dendritic [...] Read more.

In 1931, Von Euler and Gaddum isolated substance P (SP), an undecapeptide from the tachykinin family, from equine brain and intestine tissue extracts. Numerous types of cells, including neurons, astrocytes, microglia, epithelial, and endothelial cells, as well as immune cells including T-cells, dendritic cells, and eosinophils, are responsible for its production. The corneal epithelium, immune cells, keratocytes, and neurons all express the two isoforms of NK1R, which has the highest affinity for SP. The most recent research supports SP’s contribution to corneal healing by encouraging epithelial cell migration and proliferation. Additionally, when applied to the eyes, SP has proinflammatory effects that result in miosis, intraocular inflammation, and conjunctival hyperemia. In this review article, we examine the role of substance P within the eye. We focus on the role of SP with regards to maintenance and healing of the corneal epithelium. Full article

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Journal of Clinical & Translational Ophthalmology

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