Transcorneal permeation has traditionally been the mechanism by which topically applied ophthalmic drugs are believed to gain access to the internal ocular structures. Relatively little attention has been given to alternate routes by which drugs may enter the eye. A system has been developed which allowed the investigation in vivo of the contribution of noncorneal absorption to intraocular drug levels after topical dosing. Using timolol and inulin as probe drugs, it was shown that the noncorneal absorption route may contribute significantly to drug penetration into intraocular tissues. Furthermore, results demonstrated that drugs absorbed by the noncorneal route appeared to enter certain intraocular tissues by a mechanism which bypasses the anterior chamber. These studies suggested that intraocular penetration via noncorneal routes involves penetration of drug across the conjunctiva/sclera. Neither reentry from the general circulation after drug absorption into the blood or drug delivery by the local vasculature accounted for the observed results. In terms of topical ophthalmic drug delivery, the noncorneal absorption route may be important for drugs that are poorly absorbed across the cornea due to their physical-chemical properties. We have demonstrated this using inulin as a model for a poorly absorbed, high molecular weight substance.
A series of 14 patients with a carotid-ophthalmic artery aneurysm were treated operatively. In five patients the aneurysms were large, but only one of these had ruptured; four of these patients had symptoms of mass lesions. The remaining nine patients were operated on for a ruptured aneurysm; seven had subarachnoid hemorrhage due to the carotid-ophthalmic artery aneurysm and two had bleeding from another aneurysm in the presence of an asymptomatic carotid-ophthalmic artery aneurysm. All patients were treated by a combined epi- and subdural direct surgical approach, which excluded the carotid-ophthalmic artery aneurysm from the circulation and made possible the preservation of the adjacent structures. Two patients died: one a few hours after surgery from a massive thromboembolism of the pulmonary artery and another 2 months after surgery as a result of gastrointestinal bleeding. All the other patients showed postoperative improvement in symptoms and signs. This report focuses on a modified direct surgical approach involving exposure of the internal carotid artery proximal to the lesion, and of the ophthalmic artery, which is of primary importance in securing safe and complete occlusion of a carotid-ophthalmic artery aneurysm. Removal of individual bone structures at the base of the skull provides a better and safer exposure of the central segment of the internal carotid artery than does excessive and hazardous retraction of the brain.
The clinical, radiographic, and anatomical features in 80 patients with ophthalmic segment aneurysms were reviewed, and were categorized according to a presumed origin related to the ophthalmic (41 cases) or superior hypophyseal (39 cases) arteries. There was a marked female predominance (7:1) and high incidence of multiple aneurysms (45%) within this population. Clinical presentations included subarachnoid hemorrhage in 23 cases (29%) and visual deficits in 24 (30%); five patients exhibited both hemorrhage and visual loss. Twenty-eight aneurysms were incidentally identified. Ophthalmic artery aneurysms arose from the internal carotid artery (ICA) just distal to the ophthalmic artery, pointed superiorly or superomedially, and (when large) deflected the carotid artery posteriorly and inferiorly, closing the siphon. Abnormalities relating to vision were not identified until the aneurysm realized giant proportions. The optic nerve was typically displaced superomedially, which restricted contralateral extension until late in the clinical course; unilateral nasal field loss was seen in 12 patients. Nine patients had bilateral ophthalmic artery aneurysms which were often clipped via a unilateral craniotomy. Superior hypophyseal artery aneurysms arose just above the dural ring from the medial bend of the ICA, at the site of perforator origin to the superior aspect of the hypophysis, and had no direct association with the ophthalmic artery. The carotid artery was usually located lateral or superolateral relative to the aneurysm. These lesions could extend medially beneath the chiasm (suprasellar variant), producing a clinical and computerized tomography picture similar to a pituitary adenoma, or they could extend ventrally to burrow beneath the anterior clinoid process (paraclinoid variant). Preoperative categorization of these lesions according to their likely branch of origin provides excellent correlation with visual deficits and operative findings, and has allowed the author to clip 52 of 54 lesions, with very low operative or visual morbidity.
STUDY DESIGN: A retrospective review of 3450 spinal surgeries was performed. OBJECTIVES: To review ophthalmic complications and their etiologies, as well as treatments and outcomes, in patients who have undergone spinal surgery. SUMMARY OF BACKGROUND DATA: Ophthalmic complications after major spinal reconstructive surgery are rare and have not been adequately addressed in the orthopedic literature. METHODS: In a series of 3450 spinal surgeries at three institutions, the authors identified seven patients (incidence = 0.20%) whose postoperative course was complicated by loss of visual acuity. These perioperative ophthalmic complications included posterior optic nerve ischemia, occipital lobe infarcts, and central retinal vein thrombosis. Operative time, estimated blood loss, and medical history of peripheral vascular, cardiovascular, or ophthalmic disease were obtained from the charts, as were follow-up data. RESULTS: Three patients recovered completely, and one had partial return of visual function. In the remaining three patients, significant visual loss persisted. CONCLUSIONS: The risk of ophthalmic complications with spinal surgery has not been fully appreciated. Because ophthalmic complications in spinal surgery may be reversed with prompt recognition and intervention, it is important for clinicians to be aware of their possible occurrence.
SUMMARY Fungi may infect the cornea, orbit and other ocular structures. Species of Fusarium , Aspergillus , Candida , dematiaceous fungi, and Scedosporium predominate. Diagnosis is aided by recognition of typical clinical features and by direct microscopic detection of fungi in scrapes, biopsy specimens, and other samples. Culture confirms the diagnosis. Histopathological, immunohistochemical, or DNA-based tests may also be needed. Pathogenesis involves agent (invasiveness, toxigenicity) and host factors. Specific antifungal therapy is instituted as soon as the diagnosis is made. Amphotericin B by various routes is the mainstay of treatment for life-threatening and severe ophthalmic mycoses. Topical natamycin is usually the first choice for filamentous fungal keratitis, and topical amphotericin B is the first choice for yeast keratitis. Increasingly, the triazoles itraconazole and fluconazole are being evaluated as therapeutic options in ophthalmic mycoses. Medical therapy alone does not usually suffice for invasive fungal orbital infections, scleritis, and keratitis due to Fusarium spp., Lasiodiplodia theobromae , and Pythium insidiosum . Surgical debridement is essential in orbital infections, while various surgical procedures may be required for other infections not responding to medical therapy. Corticosteroids are contraindicated in most ophthalmic mycoses; therefore, other methods are being sought to control inflammatory tissue damage. Fungal infections following ophthalmic surgical procedures, in patients with AIDS, and due to use of various ocular biomaterials are unique subsets of ophthalmic mycoses. Future research needs to focus on the development of rapid, species-specific diagnostic aids, broad-spectrum fungicidal compounds that are active by various routes, and therapeutic modalities which curtail the harmful effects of fungus- and host tissue-derived factors.
Importance: ChatGPT is an artificial intelligence (AI) chatbot that has significant societal implications. Training curricula using AI are being developed in medicine, and the performance of chatbots in ophthalmology has not been characterized. Objective: To assess the performance of ChatGPT in answering practice questions for board certification in ophthalmology. Design, Setting, and Participants: This cross-sectional study used a consecutive sample of text-based multiple-choice questions provided by the OphthoQuestions practice question bank for board certification examination preparation. Of 166 available multiple-choice questions, 125 (75%) were text-based. Exposures: ChatGPT answered questions from January 9 to 16, 2023, and on February 17, 2023. Main Outcomes and Measures: Our primary outcome was the number of board certification examination practice questions that ChatGPT answered correctly. Our secondary outcomes were the proportion of questions for which ChatGPT provided additional explanations, the mean length of questions and responses provided by ChatGPT, the performance of ChatGPT in answering questions without multiple-choice options, and changes in performance over time. Results: In January 2023, ChatGPT correctly answered 58 of 125 questions (46%). ChatGPT's performance was the best in the category general medicine (11/14; 79%) and poorest in retina and vitreous (0%). The proportion of questions for which ChatGPT provided additional explanations was similar between questions answered correctly and incorrectly (difference, 5.82%; 95% CI, -11.0% to 22.0%; χ21 = 0.45; P = .51). The mean length of questions was similar between questions answered correctly and incorrectly (difference, 21.4 characters; SE, 36.8; 95% CI, -51.4 to 94.3; t = 0.58; df = 123; P = .22). The mean length of responses was similar between questions answered correctly and incorrectly (difference, -80.0 characters; SE, 65.4; 95% CI, -209.5 to 49.5; t = -1.22; df = 123; P = .22). ChatGPT selected the same multiple-choice response as the most common answer provided by ophthalmology trainees on OphthoQuestions 44% of the time. In February 2023, ChatGPT provided a correct response to 73 of 125 multiple-choice questions (58%) and 42 of 78 stand-alone questions (54%) without multiple-choice options. Conclusions and Relevance: ChatGPT answered approximately half of questions correctly in the OphthoQuestions free trial for ophthalmic board certification preparation. Medical professionals and trainees should appreciate the advances of AI in medicine while acknowledging that ChatGPT as used in this investigation did not answer sufficient multiple-choice questions correctly for it to provide substantial assistance in preparing for board certification at this time.
PURPOSE: Currently available ophthalmic drug delivery systems are inefficient and may lead to side effects. To increase efficiency and reduce side effects, the authors propose disposable particle-laden soft contact lenses for ophthalmic drug delivery. METHODS: The essential idea is to encapsulate the ophthalmic drug formulations in nanoparticles and to disperse these drug-laden particles in the lens material, such as poly-2-hydroxyethyl methacrylate (p-HEMA) hydrogels. The drug-laden p-HEMA hydrogels were synthesized by free radical solution polymerization of the monomers in presence of nanoparticles. The particle-laden hydrogels were characterized by light-transmission and electron microscopy studies. Release profiles of lidocaine, a model hydrophobic drug, were measured by UV-Vis spectrophotometry. RESULTS: Microemulsions of hexadecane in water stabilized with a silica shell around the particles produced transparent hydrogels. Contact lenses made with particle-laden hydrogels released therapeutic levels of drug for a few days. CONCLUSIONS: Particle-laden hydrogels are promising candidates for ophthalmic drug delivery. They are transparent and can release drugs for extended periods. The drug delivery rates can be controlled by varying the loading of nanoparticles in the gel.
BACKGROUND/AIMS: Tuberous sclerosis complex (TSC) has retinal and non-retinal ophthalmic manifestations. This study was designed to determine the prevalence of the ophthalmic manifestations and of refractive errors in a population of patients with TSC. METHODS: 179 patients identified were in a prevalence study of TSC in the south of England and 107 of these agreed to full ophthalmic examination which was successful in 100. Ophthalmic examination included examination of the eyelids, cover test, examination of the irides, dilation funduscopy using both direct and indirect ophthalmoscopy, and refraction using retinoscopy. Myopia was defined as a spherical equivalent <-0.5D and hyperopia as a spherical equivalent >+0.5D. RESULTS: Retinal hamartomas were seen in 44 of the 100 patients. The commonest morphological type of hamartoma seen was the flat, translucent lesion in 31 of the 44 patients (70%). The multinodular "mulberry" lesion was seen in 24 of the 44 patients (55%) and the transitional type lesion was seen in four of the 44 patients (9%). Punched out areas of retinal depigmentation were seen in 39 of the 100 patients but only six of 100 controls. 27% of eyes were myopic, 22% were hyperopic, and 27% had astigmatism >0.75D. Of the non-retinal findings, 39 patients had angiofibromas of the eyelids, five had non-paralytic strabismus, and three had colobomas. CONCLUSION: Apart from the higher prevalence of flat retinal hamartomas, the findings of this study compare closely with previous large clinic based series of TSC patients. Refractive findings were similar to previous studies of a similarly aged non-TSC population. This is the first series to document the statistically significant association of punched out chorioretinal depigmentation with TSC and the authors believe that it should be looked for as an aid to diagnosis.
This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments, in situ gels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to defense mechanisms of the human eye, extending contact time of drug with the cornea, increasing the penetration through the complex anatomical structure of the eye, and providing controlled release of drugs into the eye tissues, which allows reducing the drug application frequency. The rest of the paper describes recommended in vitro and in vivo studies to be performed for various ophthalmic drugs forms in order to assess whether the form is acceptable from the perspective of desired properties and patient's compliance.
PURPOSE: To study the effectiveness of combined systemic chemotherapy and local ophthalmic therapy for retinoblastoma with the goal of avoiding enucleation and external-beam radiation therapy (EBRT). PATIENTS AND METHODS: This was a prospective, nonrandomized, single-arm clinical trial. Seventy-five eyes were followed in 47 children. Patients were treated with a six-cycle protocol of vincristine, etoposide, and carboplatin. Most (83%) also received ophthalmic treatment (cryotherapy, laser photocoagulation, thermotherapy, or plaque radiation therapy) during and/or after the chemotherapy. RESULTS: With a median follow-up of 13 months, event-free survival was 74%, with an event defined as enucleation and/or EBRT. Six children required EBRT in seven eyes (9%); five required enucleation of one eye (7%); five required a combination of EBRT and enucleation in six eyes (8%). Reese-Ellsworth groups 1, 2, and 3 eyes had excellent results, with avoidance of EBRT or enucleation in all 39. Treatment of groups 4 and 5 was less successful, with 33% of six eyes and 53% of 30 eyes, respectively, requiring EBRT and/or enucleation. Toxicities from chemotherapy were mild and included cytopenias (89%), fever and neutropenia (28%), infection (9%), and gastrointestinal symptoms, dehydration, and vincristine neurotoxicity (40%). No patients developed a second malignancy, metastatic disease, renal disease, or ototoxicity. CONCLUSION: In retinoblastoma patients with Reese-Ellsworth eye groups 1, 2, or 3, systemic chemotherapy used with local ophthalmic therapies can eliminate the need for enucleation or EBRT without significant systemic toxicity. More effective therapy is required for Reese-Ellsworth eye groups 4 and 5.
PURPOSE: The aim of this article was to systematically review all the available ophthalmic patient-reported outcome (PRO) instruments (questionnaires) that demonstrated interval measurement properties to identify the instruments with the highest psychometric quality for use in different eye diseases and conditions. METHODS: An extensive literature review was carried out to identify all existing ophthalmic PRO instruments. Instruments were then excluded if they did not have demonstrable interval measurement properties; the remaining instruments were reviewed. The quality of the following psychometric properties was assessed: content development (initial item development process), performance of the response scale, dimensionality (whether the instrument measures a single construct), measurement precision, validity (convergent, concurrent, discriminant, and known groups), reliability (test-retest), targeting (whether the items are appropriate [e.g., difficulty level] for the population), differential item functioning (whether subgroups of people respond differently to an item), and responsiveness. RESULTS: The search identified 48 PRO instruments that demonstrated interval measurement properties, and these were relevant to nine applications: glaucoma, dry eye, refractive errors, cataract, amblyopia and strabismus, macular diseases, adult low vision, children low vision, and others. These instruments were evaluated against the psychometric property quality criteria and were rated for quality based on the number of criteria met. CONCLUSIONS: This review provides a descriptive catalog of ophthalmic PRO instruments to inform researchers and clinicians on the choice of the highest-quality PRO instrument suitable for their purpose.
B-Scan-guided, pulsed Doppler ultrasonography of central retinal vessels and ophthalmic arteries of 72 normal subjects gave the following average peak flow velocities: central retinal artery, 9.5 +/- 3.1 cm/s; central retinal vein, 5.7 +/- 1.5 cm/s; and ophthalmic artery, 31.6 +/- 9.0 cm/s. Doppler shifts in the central retinal vessels were absent at intraocular pressures above 80 mm Hg. Ophthalmic artery systolic, middiastolic, and end-diastolic velocities significantly declined as a function of age. The technique is independent of the status of the ocular media, is noninvasive, requires little time, and causes minimal discomfort.
After discussing the rationale and assumptions of the ANSI Z136.1-2000 Standard for protection of the human eye from laser exposure, we present the concise formulation of the exposure limits expressed as maximum permissible radiant exposure (in J/cm(2)) for light overfilling the pupil. We then translate the Standard to a form that is more practical for typical ophthalmic devices or in vision research situations, implementing the special qualifications of the Standard. The safety limits are then expressed as radiant power (watts) entering the pupil of the eye. Exposure by repetitive pulses is also addressed, as this is frequently employed in ophthalmic applications. Examples are given that will familiarize potential users with this format.
Liposomal formulations were significantly explored over the last decade for the ophthalmic drug delivery applications. These formulations are mainly composed of phosphatidylcholine (PC) and other constituents such as cholesterol and lipid-conjugated hydrophilic polymers. Liposomes are biodegradable and biocompatible in nature. Current approaches for topical delivery of liposomes are focused on improving the corneal adhesion and permeation by incorporating various bioadhesive and penetration enhancing polymers. In the case of posterior segment disorders improvement in intravitreal half life and targeted drug delivery to the retina is achieved by liposomes. In this paper we have attempted to summarize the applications of liposomes in the field of ophthalmic drug delivery by citing numerous investigators over the last decade.
We report 13 cases of ophthalmic complications resulting from dengue infection in Singapore. We performed a retrospective analysis of a series of 13 patients with dengue fever who had visual impairment. Investigations included Humphrey automated visual field analyzer, Amsler charting, fundus fluorescein angiography, and optical coherence tomography. Twenty-two eyes of 13 patients were affected. The mean age of patients was 31.7 years. Visual acuity varied from 20/25 to counting fingers only. Twelve patients (92.3%) noted central vision impairment. Onset of visual impairment coincided with the nadir of serum thrombocytopenia. Ophthalmologic findings include macular edema and blot hemorrhages (10), cotton wool spots (1), retinal vasculitis (4), exudative retinal detachment (2), and anterior uveitis (1). All patients recovered visual acuity to 20/30 or better with residual central scotoma by 12 weeks. These new complications suggest a widening spectrum of ophthalmic complications in dengue infection.
Anterior segment imaging is a rapidly advancing field of ophthalmology. New imaging modalities, such as rotating Scheimpflug imaging (Pentacam-Scheimpflug) and anterior segment optical coherence tomography (Visante OCT and Slit-Lamp OCT), have recently become commercially available. These new modalities supplement the more established imaging devices of Orbscan scanning slit topography and ultrasound biomicroscopy (UBM). All devices promise quantitative information and qualitative imaging of the cornea and anterior chamber. They provide a quantitative angle estimation by calculating the angle between the iris surface and the posterior corneal surface. Direct angle visualisation is possible with the OCT devices and UBM; they provide images of the scleral spur, ciliary body, ciliary sulcus and even canal of Schlemm in some eyes. Pentacam-Scheimpflug can measure net corneal power, a feature particularly useful for cataract patients having undergone previous corneal surgery. Anterior segment OCT can measure corneal flap depth following LASIK and anterior chamber width prior to phakic intraocular lens implantation. The arrival of the new imaging devices may herald the dawn of a new era for ophthalmic diagnosis, particularly in view of the ease and non-contact nature of examination.
Blindness and vision impairment are the most devastating global health problems resulting in a substantial economic and social burden. Delivery of drug to particular parts of the anterior or posterior segment has been a major challenge due to various protective barriers and elimination mechanisms associated with the unique anatomical and physiological nature of the ocular system. Drug administration to the eye by conventional delivery systems results in poor ocular bioavailability (<5%). The designing of a novel approach for a safe, simple, and effective ocular drug delivery is a major concern and requires innovative strategies to combat the problem. Over the past decades, several novel approaches involving different strategies have been developed to improve the ocular delivery system. Among these, the ophthalmic in-situ gel has attained a great attention over the past few years. This review discussed and summarized the recent and the promising research progress of in-situ gelling in ocular drug delivery system.
THE pioneer worker in the study of the ophthalmic artery, particularly its branches and their variations, was Meyer (1887), whose observations on twenty cases have been accepted more or less as classical for the last three- quarters of a century. No detailed investigation has since been carried out in this field and the descriptions of the branches of this artery which appear in the various text-books of anatomy and ophthalmology merely reflect his conclusions. Moreover, little information regarding the branches and their anomalies is available in the literature. It was therefore thought desirable to study this problem afresh in detail.
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