Topical Eye Drops Research Articles

Comprehensive Pharmacokinetic Evaluation of High Melanin Binder Levofloxacin in Rabbits Shows Potential of Topical Eye Drops for Posterior Segment Treatment.

The purpose of this work was to understand the impact of melanin binding on ocular pharmacokinetics after administration of a high-binder model drug via different administration routes. We applied levofloxacin to pigmented and albino rabbits as eye drops (single and multiple), as well as by intravitreal and intravenous injections. Ocular tissues and plasma were analyzed for levofloxacin concentrations with liquid chromatography-mass spectrometry (LC-MS/MS), and pharmacokinetic parameters were calculated. The data show enrichment of levofloxacin and weeks-long retention in pigmented tissues. Upon intravitreal injection, the area under the curve (AUC) values in pigmented tissues were about 9 to 15 times higher than the respective values in the albino rabbits, but this difference expanded to 255- to 951-fold following topical eye drop administration. Multiple dosing of eye drops led to substantial accumulation of levofloxacin in the pigmented tissues: AUC values were 3 to 12 times higher than after intravitreal injection. The AUCs were much lower after single topical or intravenous drug administrations. High drug levels (0.1-35 µM) were always observed in the neural retinas of pigmented eyes; the highest exposure was seen after intravitreal administration followed by multiple doses of topical drops. Single topical instillation and intravenous injections to the albino rabbits resulted in vitreal bioavailability values of 0.009% and 0.003%, respectively. Melanin binding can be used to achieve targeted drug delivery and extended retention in pigmented ocular tissues. The results from topical multiple dosing experiments suggest that eye drop treatment may yield drug exposures and responses comparable to intravitreal delivery, even in the retinal pigment epithelium and choroid.

Navigating Dry Eye Research: A Comprehensive Review of Etiology, Clinical Trials, Patents, and Recent Advancements.

Millions of people worldwide suffer from dry eye disease. Dry eye, a multifunctional condition of the ocular surface, typically occurs in conjunction with an unbalanced tear film. With increasing age, the dry eye problem becomes worse. Aqueous-deficit dry eye and evaporative dry eye are the two traditional classifications for dry eye. Various examination tools are used to diagnose dry eye. Clinical trials are conducted in four phases to check the safety and efficacy of drugs. The quick clearance from the precorneal space is ensured by the eye's advanced defense mechanism. It restricts the integrated medicine's entry into the eyes, resulting in a usually low bioavailability for topical eyedrops. In this study, we focus on recently developed formulations for curing dry eye. This review's goal was to outline the etiology, clinical discovery and development, patents, and recent advancements for dry eye disease. The current study has described the widespread incidence of dry eye, which was found to be more common as people aged and recently developed formulations are treating dry eyes. According to research, novel formulations are enhancing ocular drug delivery. In this review, etiology, clinical data, dry eye formulation patents, and recent advancements are all included.

Bilateral serous retinal detachment in HELLP syndrome associated with post-partum sepsis and acute kidney injury: A case report

Serous retinal detachment (RD) can occur either during or after pregnancy, and is often associated with hypertensive disorders in pregnancy. A variant of pre-eclampsia–atypical pre-eclampsia–may present without proteinuria or hypertension. We report a case of a 26-year-old normotensive primigravida who developed sudden blurring of vision in both her eyes during puerperium. Fundoscopy revealed serous retinal detachment in both eyes. Optical coherence tomography (OCT) demonstrated sub-retinal fluid (SRF) in both eyes, and fundus fluorescein angiography (FFA) displayed leakage with pooling of dye all over the posterior pole. She responded well to oral and topical steroid eyedrops, and topical non-steroidal anti-inflammatory eyedrops. Her best-corrected visual acuity improved within a month, with resorption of subretinal fluid. Awareness about serous retinal detachment during/after pregnancy in the absence of hypertensive disorders is noteworthy. The visual prognosis is usually favorable, and this knowledge can allay fear and anxiety among patients.

Efficacy and Safety of Pilocarpine Eye Drops Combinations for Treating Presbyopia in a Thai Population: A Randomized Crossover Trial

Objective: This study aimed to assess and compare the effectiveness and side effects of various concentrations of pilocarpine eye drops (1.5%, 1.25%, and 1%), with and without 0.1% brimonidine, in treating presbyopia, specifically in a Thai population. Materials and Methods: A prospective, randomized, double-blinded, and crossover trial was conducted at Siriraj Hospital from August 2022 to April 2023. The study included emmetropic individuals aged 40 to 60 with presbyopia (near visual acuity not exceeding J1+) and refractive errors within +/- 0.5D. The ten subjects were assigned randomly to 6 groups for the different concentrations and type of eyedrops using a computer-generated systematic randomization to receive 1.5%, 1.25%, and 1% pilocarpine with and without 0.1% brimonidine. And visual outcomes including visual acuity at distance and near were measured at 2, 4, and 6 hours post-application, with adverse effects monitored. Primary outcome was visual acuity at near after applied topical eye drops. Results: Among the 10 participants (30% male, median age 46.5 years old), 1.25% pilocarpine and combined 1.25% pilocarpine + 0.1% brimonidine significantly improved near visual acuity at all time points (statistically significant with Bonferroni correction). Adverse effects, such as dry eye and irritation, were more common with 1.5% pilocarpine + 0.1% brimonidine. Conclusion: In this preliminary study, 1.25% pilocarpine and 1.25% pilocarpine + 0.1% brimonidine showed promise in effectively treating presbyopia in the Thai study population, with acceptable side effect rates. Further research with larger sample sizes is needed to confirm these findings and provide more robust insights into presbyopia management in the Asian demographic.

Administration of Nicotine Can Inhibit Myopic Growth in Animal Models.

While previously investigating the mechanism by which atropine inhibits ocular growth, we observed that stimulation of nicotinic receptors can inhibit experimental myopia. This study expands on that preliminary finding and investigates the safety and efficacy of nicotinic stimulation in the inhibition of ocular growth. Nicotine's ability to inhibit form-deprivation myopia (FDM), following intravitreal injection (9 chicks per group) or topical application (6 chicks per group), was investigated over three doses. The ability of nicotine to inhibit lens-induced myopia (LIM) was also tested (in 12 chicks). For ocular safety, following 4weeks of topical treatment with nicotine (n = 10), pupillary reflex, intraocular pressure, corneal curvature/thickness, lens thickness, retinal health (retinal thickness/cell apoptosis), as well as retinal function (electroretinogram recordings) were assessed. We also examined the effects of nicotine on non-ocular autonomic functions in both chicks (n = 5) and mice (n = 5). Nicotine was observed to significantly inhibit the development of FDM in chicks when administered as an intravitreal injection (P<0.05) or topical eye drops (P<0.05), albeit not in a dose-dependent manner. Nicotine also inhibited LIM (P<0.05) to a similar degree to that seen for FDM. Although ocular health was (for the most part) unaffected by nicotine, the highest topical dose induced a temporary reduction in cardiorespiratory output (P<0.05). Nicotine, administered as an intravitreal injection or topical eye drop, significantly inhibits the development of experimental myopia. Although the anti-myopic effects observed presently are interesting, the well-reported side effects (expanded on presently) and addictive properties of nicotine would preclude its clinical use.

Dexamethasone acetate loaded poly(ε-caprolactone) nanofibers for rat corneal chemical burn treatment

Topical eye drop approaches to treat ocular inflammation in dry eyes often face limitations such as low efficiency and short duration of drug delivery. Nanofibers serve to overcome the limitation of the short duration of action of topical eye drops used against ocular inflammation in dry eyes. Several attempts to develop suitable nanofibers have been made; however, there is no ideal solution. Here, we developed polycaprolactone (PCL) nanofibers loaded with dexamethasone acetate (DEX), prepared by electrospinning, as a potential ocular drug delivery platform for corneal injury treatment. Thirty-nine Sprague Dawley rats (7 weeks old males) were divided into four treatment groups after alkaline burns of the cornea; negative control (no treatment group); dexamethasone eyedrops (DEX group); PCL fiber (PCL group); dexamethasone loaded PCL (PCL + DEX group). We evaluated therapeutic efficacy of PCL + DEX by examining the epithelial wound healing effect, the extent of corneal opacity and neovascularization. Additionally, various inflammatory factors, including IL-1β, were investigated through immunochemistry, western blot analysis, and quantitative real-time RT-PCR (qRT-PCR). PCL + DEX group showed histologically alleviated signs of corneal inflammation compared with DEX group, which showed a decrease in IL-1β and MMP9 in the corneal stroma. The quantitative expression on day 1 after alkaline burn of pro-inflammatory markers, including IL-1β and IL-6, in the PCL + DEX group was significantly lower than that in the DEX group. Notably, PCL + DEX treatment significantly suppressed neovascularization, and enhanced the anti-inflammatory function of DEX during the acute phase of ocular inflammation. Collectively, these findings suggest that PCL + DEX may be a promising approach to effective drug delivery in corneal burn injuries.

A Case of Chronic Conjunctivitis Caused by Fusobacterium nucleatum Misdiagnosed as Inclusion Conjunctivitis

Purpose: To report a case of chronic conjunctivitis caused by &lt;i&gt;Fusobacterium nucleatum&lt;/i&gt; misdiagnosed as adult inclusion conjunctivitis.Case summary: A 48-year-old female visited our clinic complaining of conjunctival injection and discharge in her right eye that had started 9 months earlier. Slit lamp examination showed conjunctival exudates with follicular hypertrophy on the upper and lower palpebral conjunctiva of the right eye. Adult inclusion conjunctivitis was suspected, and polymerase chain reaction tests for 12 sexually transmitted infections, serum &lt;i&gt;Chlamydia trachomatis&lt;/i&gt; antibody test, sputum tests, and urine tests were performed. The serum trachomatis IgM was negative, but IgG was positive; there were no other specific findings. The patient was treated with oral doxycycline and topical antibiotics eyedrops for 1 week, but there was no improvement. &lt;i&gt;Fusobacterium nucleatum&lt;/i&gt; was detected in a conjunctival swab culture. The oral antibiotic was changed to amoxicillin/clavulanic acid. After 1 week, the symptoms improved and the chronic conjunctivitis and follicles decreased; 4 weeks later, recovery was complete.Conclusions: Chronic conjunctivitis caused by bacteria such as &lt;i&gt;Fusobacterium nucleatum&lt;/i&gt; should be considered if adult inclusion conjunctivitis is suspected and does not respond to treatment.

Ocular toxocariasis masquerading as toxoplasmosis: a case report and literature review

Background: False-negative and false-positive results in Toxoplasma serology are possible, and this could be misleading. Here, we report the case of a boy with Toxocara-associated panuveitis who was initially treated for toxoplasmosis owing to false-positive Toxoplasma immunoglobulin M (IgM) serology. Case Presentation: A nine-year-old boy presented with intermittent headaches and blurred vision in the left eye. Close contact with domesticated animals was remarkable in the patient’s history. Upon examination, vision was 20/400 in the left eye. Slit-lamp examination revealed anterior chamber cells and flare without keratic precipitates, with vitreous cells and veils, optic disc edema, and a blurred fundus appearance. A systemic investigation revealed the presence of anti-Toxoplasma IgM antibodies. Treatment was initiated using topical cycloplegic and corticosteroid eye drops, in addition to oral trimethoprim/sulfamethoxazole. Oral corticosteroids were also administered. As the inflammation resolved, an inferior tractional detachment was detected on fundus examination, leading to the ultimate diagnosis of ocular toxocariasis. An enzyme-linked immunosorbent assay was positive for serum Toxocara antibodies. A fourteen-day course of oral albendazole was ordered by the pediatric infectious disease service because of the concern for visceral larva migrans, while topical eye drops were continued and oral prednisone was tapered. One month later, visual acuity in the left eye had improved to 20/70. The anterior chamber inflammation resolved; however, some vitreous cells and optic disc edema persisted. The inferior tractional detachment was much better visualized, and a peripheral granuloma was observed. Four months later, without any oral or topical medications, the patient’s visual acuity had improved to 20/30 and his eye had no active inflammation. The patient has been followed up for two years and has never developed any other lesions. Conclusions: False-positive results on Toxoplasma serology and diffuse vitritis from toxocariasis that limited retinal visualization complicated the initial diagnosis in this case. In diagnosing the etiology of uveitis, ocular examination and detailed history taking should be emphasized, as laboratory results may be misleading.

Topical three-drug combination in the management of pseudophakic cystoid macular edema

The purpose was to report the outcome after usage of three topical eyedrops combination, consisting of one steroid, one carbonic anhydrase inhibitor (CAI), and one non-steroidal anti-inflammatory drug (NSAID) in the treatment of pseudophakic cystoid macula edema (PCME) or Irvine–Gass syndrome. Treatment response monitoring of two patients with PCME to the combination of three eyedrops in a fixed dose regimen done using Optical Coherence Tomography. In both cases, significant improvement was documented within 1 week of starting the treatment, with respect to both visual acuity as well as central macular thickness and intraretinal fluid or cystoid macula edema (CME) resolution. The combination of three topical drugs of difluprednate (steroid), dorzolamide (CAI), and nepafenac (NSAID) is highly effective in treating select cases of pseudophakic CME and negates the need for usage of intravitreal (IVT) or posterior sub-Tenon’s injection of drugs such as triamcinolone acetonide, i.e., IVT triamcinolone acetonide, or posterior subtenon thus avoiding its associated complications.

The effect of intense pulsed light combined with topical 0.05% Cyclosporin A eyedrops in the treatment of Sjögren’s syndrome related dry eye

ABSTRACT Objectives This study aimed to assess the effectiveness and safety of intense pulsed light (IPL) therapy plus topical 0.05% cyclosporine A (CsA) eye drops to treat Sjögren’s Syndrome-related dry eyes (SS-DE). Research design and methods In this prospective, randomized trial included, 60 individuals with SS-DE symptoms were randomized to receive topical eye drops containing either 0.1% sodium hyaluronate (Group S) or 0.05% CsA (Group C) plus IPL therapy. Before the first treatment (baseline), and at 12, 16, and 20 weeks after treatment commencement, we assessed the best corrected visual acuity (BCVA), the Ocular Surface Disease Index (OSDI) score, the Schirmer I test (SIT), noninvasive tear breakup time (NBUT), corneal fluorescein staining (CFS), meibomian gland (MG) dropout, lid margin abnormality, MG expressibility, and meibum quality. Results Both groups showed significant improvements in the OSDI, NBUT, CFS, MG expressibility, and meibum quality (all p < 0.05). Group C showed a greater increase in OSDI, NBUT, MG expressibility, and meibum quality (all p < 0.05). Moreover, SIT and lid margin abnormalities significantly improved in Group C (both p < 0.05), but not in Group S. Conclusion Treatment with 0.05% CsA eyedrops plus IPL therapy could significantly reduce the issues and physical discomfort of patients with SS-DE. Clinical Trial Registered on 20 July 2021, with the registration number ChiCTR2100049059.

Adherence to Cysteamine Therapy Among Patients Diagnosed with Cystinosis in Saudi Arabia: A Prospective Cohort Study.

Cystinosis is a rare autosomal recessive disorder in which cystine crystals accumulate within the cellular lysosomes, causing damage to multiple organs. Due to challenges with the stringent cysteamine treatment regimen and side effects, adherence is often sub-optimal. This study aimed to assess the level of adherence to cysteamine therapy among cystinosis patients in Saudi Arabia and its impact on their quality of life. Electronic medical record data of 39 cystinosis patients from the Department of Nephrology at King Faisal Specialist Hospital and Research Center in Saudi Arabia were reviewed, and 25 patients were included in this study. Out of the 25 patients included in the final analysis, 64% (n = 16) were female. The mean age was 19.04 years. Almost all patients (23/25, 92%) were on oral IR cysteamine therapy, and 52% (13/25) were on topical cysteamine eye drop treatment. Of the 15 patients who responded to the Morisky Medication Adherence Scale-8 (MMAS-8) questionnaire, only 4 (26.7%) were highly adherent to cysteamine therapy. Most of the respondents (7/15, 46.7%) showed a medium level of treatment adherence. Based on the medication possession ratio for oral cysteamine, only 6 out of 23 patients (26.1%) were found to be 96-100% adherent. For the cysteamine eye drops, only 5/13 patients (38.4%) were 76-95% adherent. The 36-Item Short Form Health Survey (SF-36) used to assess patients' health-related outcomes showed that their quality of life was affected in the domains of 'social functioning' and 'energy/fatigue.' Despite a small sample size, this study shows sub-optimal adherence to cysteamine treatment in patients from Saudi Arabia. The possible reasons for low treatment adherence could be a high frequency of administration and treatment-related side effects.

De novo manifestations during adalimumab treatment in Behçet's syndrome.

Treatment response may be variable across organ manifestations of Behçet syndrome (BS). We aimed to determine the frequency of de novo manifestations during adalimumab treatment. We conducted a chart review of all BS patients who received adalimumab in our center between 2008 and 2023. Demographic data, reasons for initiating adalimumab, concurrent medications, previous treatments, and outcomes were recorded. We defined de novo manifestations as new BS manifestations that occurred for the first time during treatment with adalimumab. For patients with vascular involvement, a new vascular event at another vessel was also considered as a de novo manifestation. Among the 335 patients, a de novo manifestation developed in 14 (4%) patients. De novo manifestations were vascular involvement in 5 patients, arthritis in 3, anterior uveitis in 2, nervous system involvement in 2, gastrointestinal involvement in 1, and epididymitis in 1 patient. The primary reasons for adalimumab treatment were vascular involvement in 5 patients, uveitis in 4, arthritis in 3, mucocutaneous involvement in 1, and epididymitis in 1 patient. Upon the development of de novo manifestation, adalimumab was switched to another biologic in 4 patients, dose was intensified in 3, colchicine, conventional immunosuppressives, and/or glucocorticoids were added in 5, and topical eye drops were added in 2 patients, leading to remission of de novo manifestations in all patients. De novo manifestations were infrequent (4%) among BS patients treated with adalimumab. Of these, 57% were major organ involvement, mainly vascular involvement. None of the patients developed posterior uveitis.

Clinical value of endoscopic lacrimal duct probing in neonates with acute dacryocystitis

ObjectiveTo observe the clinical of endoscopic-assisted lacrimal duct probing in neonates with acute dacryocystitis. MethodsThe prospective treatment of 148 eyes of 103 cases of neonatal acute dacryocystitis was studied. In the observation group, 58 cases (76 eyes) underwent endoscopic exploration of lacrimal passage under topical anesthesia. Make the child lie on the bed, after the surface anesthesia of hydroxybucaine hydrochloride, dot dilator is not easy to expose the dilatable lower point. With the assistance of nasal endoscope, the probe of the No. 6 lateral foramina lacrimal duct entered the lacrimal duct and dacryocyst successively. After entering the dacryocyst, the pus was sucked out with a syringe and rinsed repeatedly with normal saline until no obvious suppurative secretions were discharged. Postoperative topical anti-inflammatory eye drops and oral antibiotics were used. In the control group, 45 patients (72 eyes) were treated with hospitalized systemic antibiotics and conservative treatment with local antibiotic eye drops. ResultsIn the observation group, 58 cases (76 eyes) underwent superficial anesthesia and nasal endoscopy assisted lacrimal duct exploration and achieved satisfactory results. Stenosis of the lower nasal passage was found in one eye. In all cases, there were no serious complications during and after surgery, and no recurrence was observed for 3 months to 1 year after surgery. In the control group, 45 cases (72 eyes) of neonates with acute dacryocystitis, 10 cases with conjunctival sac secretion disappeared after conservative treatment. Redness and swelling in the dacryocystitis were improved in 31 cases, of which 2 cases had facial scars due to drainage of pus from the conjunctiva sac through a percutaneous laceration incision. Four patients were discharged automatically due to the aggravation of symptoms. After 6 months of follow-up, about 50% of the children received exploratory treatment of lacrimal passage and completely healed. ConclusionNasal endoscope-assisted dacryocystitis is a method for the treatment of neonatal acute dacryocystitis, which is worthy of clinical promotion.

Combination Nanomedicine Strategy for Preventing High-Risk Corneal Transplantation Rejection.

High-risk (HR) corneal transplantation presents a formidable challenge, with over 50% of grafts experiencing rejection despite intensive postoperative care involving frequent topical eyedrop administration up to every 2 h, gradually tapering over 6-12 months, and ongoing maintenance dosing. While clinical evidence underscores the potential benefits of inhibiting postoperative angiogenesis, effective antiangiogenesis therapy remains elusive in this context. Here, we engineered controlled-release nanomedicine formulations comprising immunosuppressants (nanoparticles) and antiangiogenesis drugs (nanowafer) and demonstrated that these formulations can prevent HR corneal transplantation rejection for at least 6 months in a clinically relevant rat model. Unlike untreated corneal grafts, which universally faced rejection within 2 weeks postsurgery, a single subconjunctival injection of the long-acting immunosuppressant nanoparticle alone effectively averted graft rejection for 6 months, achieving a graft survival rate of ∼70%. Notably, the combination of an immunosuppressant nanoparticle and an anti-VEGF nanowafer yielded significantly better efficacy with a graft survival rate of >85%. The significantly enhanced efficacy demonstrated that a combination nanomedicine strategy incorporating immunosuppressants and antiangiogenesis drugs can greatly enhance the ocular drug delivery and benefit the outcome of HR corneal transplantation with increased survival rate, ensuring patient compliance and mitigating dosing frequency and toxicity concerns.

Ocular Hydrogel Materials and Corresponding Methods of Anterior Segment Drug Delivery: A Review

Ocular conditions have historically proven difficult to treat. Topical eye drops are the primary method of anterior ocular drug delivery but have demonstrated low effectiveness as they require perpetual administration to achieve adequate doses of drug in the target tissue. This can lower patient compliance and increase the risk of side effects, such as systemic toxicity as most of the drug is absorbed through the eye’s natural clearance pathways. Considering this, further development of alternate anterior delivery methods has the potential to improve drug effectiveness, residence times, and bioavailability, as well as reduce systemic toxicity. To this end, the ongoing development of contact lenses, thermogels, nanoparticle delivery systems, as well as mucoadhesive and mucopenetrative properties are being explored. This paper will discuss these developments, as well as their implications in ocular treatment.

Evaluation of the Ocular Safety of Hollow Mesoporous Organosilica Nanoparticles with Different Tetrasulfur Bond Content.

Drug therapy for eye diseases has been limited by multiple protective mechanisms of the eye, which can be improved using well-designed drug delivery systems. Mesoporous silica nanoparticles (MSNs) had been used in many studies as carriers of therapeutic agents for ocular diseases treatment. However, no studies have focused on ocular biosafety. Considering that MSNs containing tetrasulfur bonds have unique advantages and have drawn increasing attention in drug delivery systems, it is necessary to explore the ocular biosafety of tetrasulfur bonds before their widespread application as ophthalmic drug carriers. In this study, hollow mesoporous silica nanoparticles (HMSNs) with different tetrasulfur bond contents were prepared and characterized. The ocular biosafety of HMSN-E was evaluated in vitro on the three selected ocular cell lines, including corneal epithelial cells, lens epithelial cells and retinal endothelial cells (HREC), and in vivo by using topical eye drops and intravitreal injections. In cellular experiments, HMSNs caused obvious S content-dependent cytotoxic effect. HMSNs with the highest tetrasulfur bond content (HMSN-E), showed the highest cytotoxicity among all the HMSNs, and HREC was the most vulnerable cell to HMSN-E. It was shown that HMSN-E could react with intracellular GSH to generate H2S and decrease intracellular GSH concentration. Treatment of HREC with HMSN-E increased intracellular ROS, decreased mitochondrial membrane potential, and induced cell cycle arrest at the G1/S checkpoint, finally caused apoptosis and necrosis of HREC. Topical eye drops of HMSN-E could cause corneal damage. The intravitreal injection of HMSN-E could induce inflammation in the vitreum and ganglion cell layers, resulting in vitreous opacities and retinal abnormalities. The incorporation of tetrasulfur bonds into HMSN can have toxic effects on ocular tissues. Therefore, when mesoporous silica nanocarriers are designed for ophthalmic pharmaceuticals, the ocular toxicity of the tetrasulfur bonds should be considered.

Improving corneal permeability of dexamethasone using penetration enhancing agents: First step towards achieving topical drug delivery to the retina

With an ever-increasing burden of vision loss caused by diseases of the posterior ocular segment, there is an unmet clinical need for non-invasive treatment strategies. Topical drug application using eye drops suffers from low to negligible bioavailability to the posterior segment as a result of static and dynamic defensive ocular barriers to penetration, while invasive delivery systems are expensive to administer and suffer potentially severe complications. As the cornea is the main anatomical barrier to uptake of topically applied drugs from the ocular surface, we present an approach to increase corneal permeability of a corticosteroid, dexamethasone sodium-phosphate (DSP), using a novel penetration enhancing agent (PEA). We synthesised a novel polyacetylene (pAc) polymer and compared its activity to two previously described cell penetrating peptide (CPP) based PEAs, TAT and penetratin, with respect to increasing transcorneal permeability of DSP in a rapid ex-vivo porcine corneal assay over 60 min. The transcorneal apparent permeability coefficients (Papp) for diffusion of pAc, and fluorescein isothiocyanate (FITC) conjugated TAT and penetratin were up to 5 times higher (p < 0.001), when compared to controls. When pAc was used in formulation with DSP, an almost 5-fold significant increase was observed in Papp of DSP across the cornea (p = 0.0130), a significant 6-fold increase with TAT (p = 0.0377), and almost 7-fold mean increase with penetratin (p = 0.9540). Furthermore, we investigated whether the PEAs caused any irreversible damage to the barrier integrity of the corneal epithelium by measuring transepithelial electrical resistance (TEER) and immunostaining of tight junction proteins using zonula occludens-1 (ZO-1) and occludin antibodies. There was no damage or structural toxicity, and the barrier integrity was preserved after PEA application. Finally, an in-vitro cytotoxicity assessment of all PEAs in human retinal pigment epithelium cells (ARPE-19) demonstrated that all PEAs were very well-tolerated, with IC50 values of 64.79 mM for pAc and 1335.45 µM and 87.26 µM for TAT and penetratin, respectively. Our results suggest that this drug delivery technology could potentially be used to achieve a significantly higher intraocular therapeutic bioavailability after topical eye drop administration, than currently afforded.

Topical glaucoma medications - Possible implications on the meibomian glands.

One of the most common causes of blindness on a global scale is glaucoma. There is a strong association between glaucoma and increased intraocular pressure (IOP). Because of this, adequate IOP-lowering is the most important treatment strategy, mostly through topical eyedrops. Well-functioning meibomian glands are paramount for maintaining a stable tear film, and their dysfunction is the most common cause of dry eye disease. There is a growing concern that both topical glaucoma medications themselves and their added preservatives damage the meibomian glands, and consequently, the ocular surface. Preserved topical glaucoma medications appear to cause dysfunction and atrophy of the meibomian glands. Upon comparison, preserved formulations caused more symptoms of dry eye, tear film instability, inflammatory changes and meibomian gland dropout than the preservative-free counterpart. However, although seemingly less detrimental, unpreserved alternatives may diminish glandular efficacy, and, depending on the active ingredient, lead to glandular death. This negatively impacts quality of life, adherence to treatment regimens and prognosis. In this review, we explore the available evidence regarding the effects of IOP-lowering eye drops on the meibomian glands.

Topical insulin for refractory persistent corneal epithelial defects

The aim was clinical evaluation of the efficacy of topical insulin eye drops in patients with refractory persistent epithelial defects (PEDs). This prospective non-randomized investigation was conducted to examine the efficacy of insulin eye drops in treating patients with PEDs that did not respond to conventional therapy. A total of twenty-three patients were included in the study, and they were administered insulin eye drops formulated as 1 U/mL, four times a day. The rate of epithelial defect resolution and time to complete corneal re-epithelialization were considered primary outcome measures. The relative prognostic impact of initial wound size and other parameters, including age, sex, smoking, diabetes, and hypertension were also analyzed. The results showed that during follow-up (maximum 50 days), a total of 16 patients (69.6%) achieved improvement. Insulin eye drops significantly reduced the corneal wounding area in 75% of patients with small epithelial defects (5.5 mm2 or less) during 20 days. Only 61% of patients with moderate epithelial defects (5.51–16 mm2) showed a significant recovery in 20–30 days. Also, 71% of patients with a defect size greater than 16 mm2, demonstrated a significant improvement in the rate of corneal epithelial wound healing in about 50 days. In conclusion topical insulin reduces the PED area and accelerates the ocular surface epithelium wound healing.

Glaucoma treatment and deprivation: time-series analysis of general practice prescribing in England.

Despite advances in glaucoma management, topical eyedrop treatment has been paramount, with prostaglandin analogues (PGAs) being first-line agents. While late presentation is linked with deprivation, there is no recent research examining associations between deprivation and prescribing within primary care. To explore PGA prescribing in general practice over a 6-year timeline, assessing associations with deprivation. Analysis of NHS Business Services Authority (NHSBSA) data for general practice prescribing in England from April 2016-March 2022. Glaucoma treatments by GP prescribers were extracted, identifying ~9.11-9.58 million prescriptions/annum. Data were linked to Index of Multiple Deprivation (IMD) quintiles of GP practices. Crude rates per 1000 population were calculated using population data from NHS Digital. Time-series analyses facilitated comparison in prescribing nationally and in deprived areas. Autoregressive Integrated Moving Average (ARIMA) modelling facilitated measurement of synchrony between time series using cross correlation. PGAs and fixed combination eyedrops accounted for approximately two-thirds of glaucoma-related prescribing. Prescriptions per month increased slightly over a 6-year timeline, but rates per 1000 population reduced in 2020-2021 during the COVID-19 pandemic. The number of PGA prescriptions dispensed in deprived areas was lower than all other quintiles. Cross-correlation analysis indicates a lag of ~12 months between average PGA prescribing nationally versus more deprived areas. The rate of PGA prescribing in primary care was substantially lower in deprived versus affluent areas, with delayed uptake of PGAs in more deprived areas of ~12 months. Further research is needed to explore reasons for this discrepancy, permitting strategies to be developed to reduce unwarranted variation.