Emory Eye Center

PurposeTo establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data.DesignConsensus meeting.ParticipantsAn international panel of retina specialists, imaging and image reading center experts, and ocular pathologists.MethodsDuring several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components.Main Outcome MeasuresA consensus classification of neovascular AMD.ResultsThe study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated.ConclusionsThe framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice. To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data. Consensus meeting. An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists. During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components. A consensus classification of neovascular AMD. The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated. The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.

A retrospective study was conducted of 308 eyes with pathologic myopia obtained from 202 patients (23 surgical eyes; 285 post mortem eyes) over a 67-year period. Histopathologic findings and percentage of eyes affected, in decreasing order of frequency, were myopic configuration of the optic nerve head, 37.7%; posterior staphyloma, 35.4%; degenerative changes of the vitreous, 35.1%; cobblestone degeneration, 14.3%; myopic degeneration of the retina, 11.4%; retinal detachment, 11.4%; retinal pits, holes, or tears, 8.1%; subretinal neovascularization, 5.2%; lattice degeneration, 4.9%; Fuchs spot, 3.2%; and lacquer cracks, 0.6%. The reasons for enucleation in the surgically obtained eyes included, in decreasing order of frequency: degeneration after retinal detachment; secondary glaucoma; endophthalmitis; postsurgical epithelial ingrowth; expulsive hemorrhage; degeneration after cataract extraction; and presumed intraocular tumor. Clinicopathologic correlations are discussed.

PURPOSE: To analyze the reasons for patient dissatisfaction after phacoemulsification with multifocal intraocular lens (IOL) implantation and the outcomes after intervention. SETTING: Emory Eye Center, Atlanta, Georgia, USA. METHODS: This retrospective review comprised eyes of patients dissatisfied with visual outcomes after multifocal IOL implantation. Outcomes analyzed included type of visual complaint, treatment modality for each complaint, and degree of clinical improvement after intervention. RESULTS: Thirty-two patients (43 eyes) reported unwanted visual symptoms after multifocal IOL implantation, including in 28 eyes (65%) with an AcrySof ReSTOR IOL and 15 (35%) with a ReZoom IOL. Thirty patients (41 eyes) reported blurred vision, 15 (18 eyes) reported photic phenomena, and 13 (16 eyes) reported both. Causes of blurred vision included ametropia (12 eyes, 29%), dry eye syndrome (6 eyes, 15%), posterior capsule opacification (PCO) (22 eyes, 54%), and unexplained etiology (1 eye, 2%). Causes of photic phenomena included IOL decentration (2 eyes, 12%), retained lens fragment (1 eye, 6%), PCO (12 eyes, 66%), dry-eye syndrome (1 eye, 2%), and unexplained etiology (2 eyes, 11%). Photic phenomena attributed to PCO also caused blurred vision. Thirty-five eyes (81%) had improvement with conservative treatment. Five eyes (12%) did not have improvement despite treatment combinations. Three eyes (7%) required IOL exchange. CONCLUSIONS: Complaints of blurred vision and photic phenomena after multifocal IOL implantation were effectively managed with appropriate treatment. Few eyes (7%) required IOL exchange. Neodymium:YAG capsulotomy should be delayed until it has been determined that IOL exchange will not be necessary.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

Drug delivery to the eye is hampered by anatomical factors, including the corneal epithelium, the blood-aqueous barrier and the blood-retinal barrier. This review aims to outline the major routes of ocular drug delivery, including systemic, topical, periocular and intravitreal. The pharmacokinetics, the disadvantages and the clinical relevance of these drug delivery routes have been emphasised. Recent advances in surgical techniques, therapeutic approaches and material sciences have produced exciting new therapies for ocular diseases. The role of ophthalmic drug formulation in targeting the desired ocular tissue and enhancing drug delivery by the chosen route whilst minimising side effects is also discussed.

The mechanism of oxidative damage to the lens through intraocular photochemical generation of superoxide and its derivatization to other oxidants such as singlet oxygen, hydroxyl radical and hydrogen peroxide has been studied. Rat lenses when organ cultured aerobically in TC 199 containing additional amounts of riboflavin were damaged as demonstrated by an inhibition of the uptake of Rb 86 against a concentration gradient. The pump was not affected by light if the culture was conducted in the basal TC 199. However, light was observed to induce significant peroxidative degradation of the tissue lipids even in the basal medium, the degradation being indicated by the formation of malonaldehyde. Both the inhibition of the pump as well as the peroxidative degradation of the tissue lipids, were attenuated considerably by scavengers of superoxide and hydrogen peroxide. In addition, the lipid degradation was prevented by vitamins C and E. The results suggest that the photodynamic injury to the lens cation pump as well as to membrane lipids is incumbent upon an initial generation of superoxide and its derivatization to other oxidants. Thus, the ocular lens is susceptible to oxidative insult and physiological damage through photocatalytic generation of various oxygen radicals. Large concentrations of ascorbic acid in the aqueous humor seems to be able to provide significant protection against such an insult. Thus, this may be one of the functions of high concentration of ascorbic acid in the aqueous humor. The implication of oxidative stress has also been examined in the genesis of cataracts in vivo. Treatment with vitamin E of the Emory mouse led to a decrease in the rate of cataract progression suggesting that at least in some instances an oxidative stress could participate in the formation of cataracts. Oxygen radicals may inflict damage at multifarious biochemical sites. Human lens lipids were also shown to have an absorption maxima at 239 nm indicating their susceptibility to oxidative degradation. In addition the lipid extract has fluorescence similar to that of lipofuscins. The levels of MDA were higher in the brunescent cataracts as compared to that in the nonbrunescent cataracts. The implications of oxidative stress towards the genesis of cataracts in humans is being explored further.

PURPOSE: To test the hypothesis that coated microneedles can deliver drugs into the eye via intrascleral and intracorneal routes in a minimally invasive manner. METHODS: Solid metal microneedles measuring 500 to 750 microm in length were coated with model drugs, protein, and DNA; inserted into nonpreserved human cadaveric sclera; and imaged. Microneedles coated with sodium fluorescein were then inserted into rabbit cornea in vivo. After needle removal, fluorescein concentration in the anterior segment of the rabbit eye was measured for 24 hours. Similar experiments were performed using pilocarpine-coated microneedles, and the rabbit pupil size was monitored afterward. RESULTS: In vitro insertion tests showed that microneedles were mechanically strong enough to penetrate into human cadaveric sclera and that the drug coating rapidly dissolved off the needles within the scleral tissue within 30 seconds after insertion. In vivo delivery from fluorescein-coated microneedles showed that fluorescein concentrations in the anterior chamber were 60 times greater than those achieved by topical application without microneedles. Similarly, microneedle delivery of pilocarpine caused rapid and extensive rabbit pupil constriction. There were no measurable inflammatory responses caused by microneedle insertion. CONCLUSIONS: This study demonstrated for the first time that coated microneedles can deliver drugs into the eye via intrascleral and intracorneal routes. This minimally invasive approach may avoid the complications associated with intraocular injection and systemic administration.

BACKGROUND: Trachoma is the world's leading cause of infectious blindness. The World Health Organization (WHO) has endorsed the SAFE strategy in order to eliminate blindness due to trachoma by 2020 through "surgery," "antibiotics," "facial cleanliness," and "environmental improvement." While the S and A components have been widely implemented, evidence and specific targets are lacking for the F and E components, of which water, sanitation, and hygiene (WASH) are critical elements. Data on the impact of WASH on trachoma are needed to support policy and program recommendations. Our objective was to systematically review the literature and conduct meta-analyses where possible to report the effects of WASH conditions on trachoma and identify research gaps. METHODS AND FINDINGS: We systematically searched PubMed, Embase, ISI Web of Knowledge, MedCarib, Lilacs, REPIDISCA, DESASTRES, and African Index Medicus databases through October 27, 2013 with no restrictions on language or year of publication. Studies were eligible for inclusion if they reported a measure of the effect of WASH on trachoma, either active disease indicated by observed signs of trachomatous inflammation or Chlamydia trachomatis infection diagnosed using PCR. We identified 86 studies that reported a measure of the effect of WASH on trachoma. To evaluate study quality, we developed a set of criteria derived from the GRADE methodology. Publication bias was assessed using funnel plots. If three or more studies reported measures of effect for a comparable WASH exposure and trachoma outcome, we conducted a random-effects meta-analysis. We conducted 15 meta-analyses for specific exposure-outcome pairs. Access to sanitation was associated with lower trachoma as measured by the presence of trachomatous inflammation-follicular or trachomatous inflammation-intense (TF/TI) (odds ratio [OR] 0.85, 95% CI 0.75-0.95) and C. trachomatis infection (OR 0.67, 95% CI 0.55-0.78). Having a clean face was significantly associated with reduced odds of TF/TI (OR 0.42, 95% CI 0.32-0.52), as were facial cleanliness indicators lack of ocular discharge (OR 0.42, 95% CI 0.23-0.61) and lack of nasal discharge (OR 0.62, 95% CI 0.52-0.72). Facial cleanliness indicators were also associated with reduced odds of C. trachomatis infection: lack of ocular discharge (OR 0.40, 95% CI 0.31-0.49) and lack of nasal discharge (OR 0.56, 95% CI 0.37-0.76). Other hygiene factors found to be significantly associated with reduced TF/TI included face washing at least once daily (OR 0.76, 95% CI 0.57-0.96), face washing at least twice daily (OR 0.85, 95% CI 0.80-0.90), soap use (OR 0.76, 95% CI 0.59-0.93), towel use (OR 0.65, 95% CI 0.53-0.78), and daily bathing practices (OR 0.76, 95% CI 0.53-0.99). Living within 1 km of a water source was not found to be significantly associated with TF/TI or C. trachomatis infection, and the use of sanitation facilities was not found to be significantly associated with TF/TI. CONCLUSIONS: We found strong evidence to support F and E components of the SAFE strategy. Though limitations included moderate to high heterogenity, low study quality, and the lack of standard definitions, these findings support the importance of WASH in trachoma elimination strategies and the need for the development of standardized approaches to measuring WASH in trachoma control programs.

PURPOSE: To complete the baseline trachoma map worldwide by conducting population-based surveys in an estimated 1238 suspected endemic districts of 34 countries. METHODS: A series of national and sub-national projects owned, managed and staffed by ministries of health, conduct house-to-house cluster random sample surveys in evaluation units, which generally correspond to "health district" size: populations of 100,000-250,000 people. In each evaluation unit, we invite all residents aged 1 year and older from h households in each of c clusters to be examined for clinical signs of trachoma, where h is the number of households that can be seen by 1 team in 1 day, and the product h × c is calculated to facilitate recruitment of 1019 children aged 1-9 years. In addition to individual-level demographic and clinical data, household-level water, sanitation and hygiene data are entered into the purpose-built LINKS application on Android smartphones, transmitted to the Cloud, and cleaned, analyzed and ministry-of-health-approved via a secure web-based portal. The main outcome measures are the evaluation unit-level prevalence of follicular trachoma in children aged 1-9 years, prevalence of trachomatous trichiasis in adults aged 15 + years, percentage of households using safe methods for disposal of human feces, and percentage of households with proximate access to water for personal hygiene purposes. RESULTS: In the first year of fieldwork, 347 field teams commenced work in 21 projects in 7 countries. CONCLUSION: With an approach that is innovative in design and scale, we aim to complete baseline mapping of trachoma throughout the world in 2015.

PURPOSE: This study seeks to determine the intraocular pharmacokinetics of molecules and particles injected into the suprachoroidal space of the rabbit eye in vivo using a hollow microneedle. METHODS: Suprachoroidal injections of fluorescein and fluorescently tagged dextrans (40 and 250 kDa), bevacizumab, and polymeric particles (20 nm to 10 μm in diameter) were performed using microneedles in New Zealand white rabbits. The fluorescence intensity within the eye was monitored in each animal using an ocular fluorophotometer to determine the distribution of the injected material in the eye over time as compared with intravitreal injection of fluorescein. Fundus photography and histology were performed as well. RESULTS: Molecules and particles injected near the limbus using a microneedle flowed circumferentially around the eye within the suprachoroidal space. By targeting the suprachoroidal space, the concentration of injected materials was at least 10-fold higher in the back of the eye tissues than in anterior tissues. In contrast, intravitreal injection of fluorescein targeted the vitreous humor with no significant selectivity for posterior versus anterior segment tissues. Half-lives in the suprachoroidal space for molecules of molecular weight from 0.3 to 250 kDa ranged from 1.2 to 7.9 hours. In contrast, particles ranging in size from 20 nm to 10 μm remained primarily in the suprachoroidal space and choroid for a period of months and did not clear the eye. No adverse effects of injection into the suprachoroidal space were observed. CONCLUSION: Injection into the suprachoroidal space using a microneedle offers a simple and minimally invasive way to target the delivery of drugs to the choroid and retina.

Macrophages can be polarized to exhibit either pro-inflammatory M1 or pro-angiogenic M2 phenotypes, but have high phenotypic plasticity. This pilot study investigated macrophage polarization in the macular retina and choroid of age-related macular degeneration (AMD) and non-AMD subjects, as well as in AMD choroidal neovascular membranes (CNVM). All specimens were evaluated for routine histopathology. Quantitative real-time polymerase chain reaction for representative M1 (CXCL11) and M2 (CCL22) transcripts were performed on macular choroidal trephines (MCT) of 19 AMD and nine non-AMD eye bank eyes, on the microdissected macular retinal cells from the archived slides of five geographic atrophic AMD, five exudative/neovascular AMD, and eight normal autopsied eyes, and on microdissected inflammatory cells from two surgically removed CNVM that did not respond to anti-vascular endothelial growth factor (VEGF) therapy. High M2-chemokine transcript and a low ratio of M1 to M2 chemokine transcript were found in aging non-AMD MCT. Advanced AMD maculae had a higher M1 to M2 chemokine transcript ratio compared to normal autopsied eyes. Macrophages in the two CNVM of patients unresponsive to anti-VEGF therapy were polarized toward either M1 or M2 phenotypes. The number of M2 macrophages was increased compared to M1 macrophages in normal aging eyes. A pathological shift of macrophage polarization may play a potential role in AMD pathogenesis.

BACKGROUND: Laser-induced thermal therapy is a promising tool in the neurosurgeon's armamentarium. This methodology has seen a resurgence in application as a result of advances in technology. OBJECTIVE: To report our initial experience with the procedure after treating 20 consecutive patients, the largest series to date. METHODS: Patients were selected for laser therapy if they had failed conventional therapies, were unable to tolerate an open cranial procedure, or the tumor was deemed otherwise inoperable. In this series, 980-nm diode laser catheters were placed stereotactically in the operating room. The patients were then transferred to the magnetic resonance imaging suite for thermal ablation. RESULTS: A total of 31 laser applicators were placed in 20 patients with intracranial neoplasms. The majority of patients (17 of 20) had prior treatment for their tumors. The overall accuracy of laser insertion was 83.9%, improving with increased experience. The average lesion volume treated was 7.0 ± 9.0 cm2. With the use of damage estimates from the software provided, the treatment continued until the entire tumor had been irreversibly ablated. The average length of hospitalization was 2.27 days, with the majority of patients going home on postoperative day 1. Complications occurred in 4 patients, typically in those who were in poor health preoperatively. CONCLUSION: Laser-induced thermal therapy is an intuitive procedure for treating difficult intracranial neoplasms. As with any other procedure, patient selection and lesion selection are important factors in determining outcome.

About one-third of patients suffering from systemic lupus erythematosus have ocular manifestations. The most common manifestation is keratoconjunctivitis sicca. The most vision threatening are retinal vasculitis and optic neuritis/neuropathy. Prompt diagnosis and treatment of eye disease is paramount as they are often associated with high levels of systemic inflammation and end-organ damage. Initial management with high-dose oral or IV corticosteroids is often necessary. Multiple "steroid-sparing" treatment options exist with the most recently studied being biologic agents.

PURPOSE OF REVIEW: To review recent clinical data on ischemic optic neuropathies, which are some of the most frequently encountered optic neuropathies. These disorders include nonarteritic anterior ischemic optic neuropathy, arteritic anterior ischemic optic neuropathy, and posterior ischemic optic neuropathy. RECENT FINDINGS: Recent studies have facilitated our understanding of the natural history of visual loss, recovery, and recurrence in these disorders. Additionally, the value of various diagnostic techniques and treatment options, particularly for arteritic anterior ischemic neuropathy, has been clarified. SUMMARY: Application of the studies described in this paper should allow the clinician to more accurately diagnose ischemic optic neuropathies and counsel the patient with regard to appropriate management, prognosis for visual recovery and future risk of recurrence.

PurposeInjection of pharmacotherapy into the suprachoroidal space, between the sclera and choroid, is an alternative delivery technique developed with the rationale of providing higher drug concentrations to posterior ocular structures compared with other intraocular and periocular injection procedures. This study was conducted to evaluate the safety and efficacy of suprachoroidally injected triamcinolone acetonide formulation (CLS-TA), a suspension of triamcinolone acetonide, in improving vision among patients with noninfectious uveitis complicated by macular edema (ME).DesignPhase 3 masked, randomized trial.ParticipantsOne hundred sixty patients with ME secondary to noninfectious uveitis. Patients were required to have a best-corrected visual acuity (BCVA) of 5 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Snellen equivalent, 20/800) and 70 or fewer ETDRS letters read (Snellen equivalent, 20/40) in the study eye.MethodsPatients were randomized 3:2 to suprachoroidally injected CLS-TA or sham treatment, with administrations at day 0 and week 12.Main Outcome MeasuresThe primary end point was improvement from baseline of 15 or more ETDRS letters in BCVA at week 24. The secondary end point was reduction from baseline in central subfield thickness (CST) at week 24.ResultsIn the CLS-TA arm, 47% of patients gained 15 or more ETDRS letters in BCVA versus 16% in the control arm (P < 0.001), meeting the primary end point. Mean reductions in CST from baseline were 153 μm versus 18 μm (P < 0.001). No serious adverse events (AEs) related to treatment were reported. Corticosteroid-associated AEs of elevated intraocular pressure occurred in 11.5% and 15.6% of the CLS-TA and control groups, respectively. Cataract AE rates were comparable (7.3% and 6.3%, respectively).ConclusionsPatients in the CLS-TA study arm experienced clinically significant improvement in vision relative to the sham procedure, demonstrating the efficacy of suprachoroidal injection of CLS-TA for the treatment of ME in a vision-threatening disorder. Injection of pharmacotherapy into the suprachoroidal space, between the sclera and choroid, is an alternative delivery technique developed with the rationale of providing higher drug concentrations to posterior ocular structures compared with other intraocular and periocular injection procedures. This study was conducted to evaluate the safety and efficacy of suprachoroidally injected triamcinolone acetonide formulation (CLS-TA), a suspension of triamcinolone acetonide, in improving vision among patients with noninfectious uveitis complicated by macular edema (ME). Phase 3 masked, randomized trial. One hundred sixty patients with ME secondary to noninfectious uveitis. Patients were required to have a best-corrected visual acuity (BCVA) of 5 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Snellen equivalent, 20/800) and 70 or fewer ETDRS letters read (Snellen equivalent, 20/40) in the study eye. Patients were randomized 3:2 to suprachoroidally injected CLS-TA or sham treatment, with administrations at day 0 and week 12. The primary end point was improvement from baseline of 15 or more ETDRS letters in BCVA at week 24. The secondary end point was reduction from baseline in central subfield thickness (CST) at week 24. In the CLS-TA arm, 47% of patients gained 15 or more ETDRS letters in BCVA versus 16% in the control arm (P < 0.001), meeting the primary end point. Mean reductions in CST from baseline were 153 μm versus 18 μm (P < 0.001). No serious adverse events (AEs) related to treatment were reported. Corticosteroid-associated AEs of elevated intraocular pressure occurred in 11.5% and 15.6% of the CLS-TA and control groups, respectively. Cataract AE rates were comparable (7.3% and 6.3%, respectively). Patients in the CLS-TA study arm experienced clinically significant improvement in vision relative to the sham procedure, demonstrating the efficacy of suprachoroidal injection of CLS-TA for the treatment of ME in a vision-threatening disorder.

INTRODUCTION: Patients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody-drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from other MMAF-containing ADCs. METHODS: Corneal examination findings from patients in DREAMM-2 were reviewed, and the clinical descriptions and accompanying images (slit lamp microscopy and in vivo confocal microscopy [IVCM]) of representative events were selected. A literature review on corneal events reported with other ADCs was performed. RESULTS: In most patients receiving single-agent belamaf (72%; 68/95), MECs were observed by slit lamp microscopy early in treatment (69% had their first event by dose 4). However, IVCM revealed hyperreflective material. Blurred vision (25%) and dry eye (15%) were commonly reported symptoms. Management of MECs included dose delays (47%)/reductions (25%), with few patients discontinuing due to MECs (1%). The first event resolved in most patients (grade ≥2 MECs and visual acuity [each 77%], blurred vision [67%], and dry eye [86%]), with no reports of permanent vision loss to date. A literature review confirmed that similar MECs were reported with other ADCs; however, event management strategies varied. The pathophysiology of MECs is unclear, though the ADC cytotoxic payload may contribute to on- or off-target effects on corneal epithelial cells. CONCLUSION: Single-agent belamaf represents a new treatment option for patients with RRMM. As with other ADCs, MECs were observed and additional research is warranted to determine their pathophysiology. A multidisciplinary approach, involving close collaboration between eye care professionals and hematologist/oncologists, is needed to determine appropriate diagnosis and management of these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT03525678.

PURPOSE: To measure the cohesive tensile strength of human LASIK corneal wounds. METHODS: Twenty-five human eye bank corneas from 13 donors that had LASIK were cut into 4-mm corneoscleral strips and dissected to expose the interface wound. Using a motorized pulling device, the force required to separate the wound was recorded. Intact and separated specimens were processed for light and electron microscopy. Five normal human eye bank corneas from 5 donors served as controls. A retrospective clinical study was done on 144 eyes that had LASIK flap-lift retreatments, providing clinical correlation. RESULTS: The mean tensile strength of the central and paracentral LASIK wounds showed minimal change in strength over time after surgery, averaging 2.4% (0.72 +/- 0.33 g/mm) of controls (30.06 +/- 2.93 g/mm). In contrast, the mean peak tensile strength of the flap wound margin gradually increased over time after surgery, reaching maximum values by 3.5 years when the average was 28.1% (8.46 +/- 4.56 g/mm) of controls. Histologic and ultrastructural correlative studies found that the plane of separation always occurred in the lamellar wound, which consisted of a hypocellular primitive stromal scar centrally and paracentrally and a hypercellular fibrotic stromal scar at the flap wound margin. The pathologic correlations demonstrated that the strongest wound margin scars had no epithelial cell ingrowth-the strongest typically being wider or more peripherally located. In contrast, the weakest wound margin scars had epithelial cell ingrowth. The clinical series demonstrated the ability to lift LASIK flaps without complications during retreatments up to 8.4 years after initial surgery, correlating well with the laboratory results. CONCLUSIONS: The human comeal stroma typically heals after LASIK in a limited and incomplete fashion; this results in a weak, central and paracentral hypocellular primitive stromal scar that averages 2.4% as strong as normal comeal stroma. Conversely, the LASIK flap wound margin heals by producing a 10-fold stronger, peripheral hypercellular fibrotic stromal scar that averages 28.1% as strong as normal comeal stromal, but displays marked variability.

INTRODUCTION: Idiopathic intracranial hypertension (IIH) is increasingly recognized as a cause of spontaneous cerebrospinal fluid (CSF) leak in the otolarnygological and neurosurgical literature. The diagnosis of IIH in patients with spontaneous CSF leaks typically is made a few weeks after surgical repair of the leak when symptoms and signs of elevated intracranial pressure (ICP) appear. METHODS: Case reports and literature review. Two young obese women developed spontaneous CSF rhinorrhea related to an empty sella in one and a cribriform plate encephalocele in the other. Both patients underwent surgical repair of the CSF leak. A few weeks later, they developed chronic headaches and bilateral papilledema. Lumbar punctures showed elevated CSF opening pressures with normal CSF contents, with temporary improvement of headaches. A man with a 3-year history of untreated IIH developed spontaneous CSF rhinorrhea. He experienced improvement of his headaches and papilledema after a CSF shunting procedure, and the rhinorrhea resolved after endoscopic repair of the leak. RESULTS: These cases and the literature review confirm a definite association between IIH and spontaneous CSF leak based on: 1) similar demographics; 2) increased ICP in some patients with spontaneous CSF leak after leak repair; 3) higher rate of leak recurrence in patients with raised ICP; 4) patients with intracranial hypertension secondary to tumors may develop CSF leak, confirming that raised ICP from other causes than IIH can cause CSF leak. CONCLUSIONS: CSF leak occasionally may keep IIH patients symptom-free; however, classic symptoms and signs of intracranial hypertension may develop after a CSF leak is repaired, exposing these patients to a high risk of recurrence of the leak unless an ICP-lowering intervention is performed.

Topical medications remain the mainstay of glaucoma treatment. This review will aim to cover the pharmacokinetics of topically applied drops, the ocular barriers to drug delivery, and the role of ophthalmic drug formulation in enhancing drug delivery to the target tissue while minimizing side effects and increasing patient compliance. Recent advances in surgical techniques, therapeutic approaches, and material sciences have produced exciting new therapies for ocular diseases. The development of new vehicles and drug formulations that require less patient compliance is also discussed, as are the routes of drug delivery for neuroprotection.

Treatment of primary intraocular uveal melanoma has developed considerably, its driver genes are largely unraveled, and the ways to assess its risk for metastases are very precise, being based on an international staging system and genetic data. Unfortunately, the risk of distant metastases, which emerge in approximately one half of all patients, is unaltered. Metastases are the leading single cause of death after uveal melanoma is diagnosed, yet no consensus exists regarding surveillance, staging, and treatment of disseminated disease, and survival has not improved until recently. The final frontier in conquering uveal melanoma lies in solving these issues to cure metastatic disease. Most studies on metastatic uveal melanoma are small, uncontrolled, retrospective, and do not report staging. Meta-analyses confirm a median overall survival of 10-13 months, and a cure rate that approaches nil, although survival exceeding 5 years is possible, estimated 2% either with first-line treatment or with best supportive care. Hepatic ultrasonography and magnetic resonance imaging as surveillance methods have a sensitivity of 95-100% and 83-100%, respectively, to detect metastases without radiation hazard according to prevailing evidence, but computed tomography is necessary for staging. No blood-based tests additional to liver function tests are generally accepted. Three validated staging systems predict, each in defined situations, overall survival after metastasis. Their essential components include measures of tumor burden, liver function, and performance status or metastasis free interval. Age and gender may additionally influence survival. Exceptional mutational events in metastases may make them susceptible to checkpoint inhibitors. In a large meta-analysis, surgical treatment was associated with 6 months longer median overall survival as compared to conventional chemotherapy and, recently, tebentafusp as first-line treatment at the first interim analysis of a randomized phase III trial likewise provided a 6 months longer median overall survival compared to investigator's choice, mostly pembrolizumab; these treatments currently apply to selected patients. Promoting dormancy of micrometastases, harmonizing surveillance protocols, promoting staging, identifying predictive factors, initiating controlled clinical trials, and standardizing reporting will be critical steppingstones in reaching the final frontier of curing metastatic uveal melanoma.