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Purpose: Pan-retinal photocoagulation (PRP) is the mainstay of treatment for proliferative diabetic retinopathy (PDR), reducing the risk of severe vision loss. Pain poses a potential obstacle to effective laser delivery and patient compliance. Therefore, implementing pain relief strategies can enhance both treatment efficacy and patient comfort., Design: A systematic review and meta-analysis., Methods: We conducted a systematic review and meta-analysis according to PRISMA guidelines. The PubMed, Embase and Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials (RCTs) that enrolled patients undergoing PRP due to DR and compared analgesics or non-steroidal anti-inflammatory drugs (NSAID) to placebo. Pain was evaluated with the visual analogue scale. The version 2 of the Cochrane Collaboration's Risk of Bias in Randomized Controlled Trials tool and its version for crossover trials were used to assess the risk of bias. The Grading of Recommendations, Assessment, Development, and Evaluation tool was used to measure the certainty of evidence., Results: A total of 13 studies were included, comprising 1404 eyes from RCTs, nine of which were crossover. Patients who were administered analgesia reported a significantly lower pain sensitivity compared to those who received placebo (Standardized mean difference [SMD] -0.38; 95% confidence interval [CI] -0.58, -0.17; P < .01; I 2 = 69%). Subgroup analysis of systemic administration of analgesics/NSAIDs (metamizole, Entonox, acetaminophen, ibuprofen, caffeine, mefenamic acid, intramuscular ketorolac tromethamine, and potassium diclofenac) also showed a statistically significant reduction in pain when compared to placebo (SMD -0.28; 95% CI -0.50, -0.07; P < .01; I 2 = 43%). Exclusive eye drops administration (ketorolac tromethamine 0.5% and sodium diclofenac 0.1%) also showed a significant difference in pain sensitivity (SMD -0.46; 95% CI -0.88, -0.05; I 2 = 83%), however with a more significant heterogeneity., Conclusions: The results of this meta-analysis including over 1000 patients demonstrated that the use of analgesics significantly reduced pain sensitivity during PRP, and systemic analgesia is potentially better than topical administration when compared to placebo., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: Chronic ocular pain (COP) is a leading cause of eye care visits in the US and has a substantial impact on quality of life and visual functioning. Although many conditions underlie COP, such as dry eye disease or post-herpetic neuralgia, some people experience pain without significant ocular signs on examination or known risk factors (eg, traumatic injury). Antidepressant medications that act primarily on the central nervous system, such as tricyclic antidepressants and serotonin and norepinephrine reuptake inhibitors, are often used to treat patients with COP, but a recent Cochrane review and network meta-analysis investigating 25 different antidepressants concluded that only two serotonin and norepinephrine reuptake inhibitors, have sufficient data to support their use in chronic pain. For all other medications, the evidence was of low certainty. We contend that while these medications are not a cure-all for chronic pain or COP, it is premature to conclude that these medications have no role in their treatment. We provide a rationale for continued use of antidepressant medications as part of a multimodal targeted treatment for patients with COP., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: For ophthalmic patients, eye discomfort is a major problem that requires efficient pain treatment techniques. Pregabalin and gabapentin have surfaced as viable treatments for post-refractive surgery pain. To manage pain after refractive surgery, gabapentin and pregabalin were evaluated in this systematic review and meta-analysis., Methodology: A thorough search of databases including PubMed, Embase, Cochrane Library, and CINAHL was performed until March 2024. Inclusion criteria were randomized controlled trials assessing pregabalin and/or gabapentin's effectiveness in treating pain post-PRK, LASIK, and LASEK surgeries., Results: Six studies met inclusion criteria, comprising a total of 391 patients undergoing various corneal surgeries. The meta-analysis revealed that pregabalin was significantly more effective than placebo in reducing pain on the first and second postoperative days (SMD day 1: -0.32, 95% CI -0.54, -0.09; SMD day 2: -0.55, 95% CI -0.85, -0.25), while gabapentin showed significant pain reduction on the second day only (SMD day 2: -0.42, 95% CI -0.71, -0.13). Combined analysis for both medications showed significant pain reduction on the first- and second-days post-surgery. No significant increase in adverse events was associated with either medication. Publication bias was minimal except for a slight asymmetry noted on day 1 effectiveness., Conclusion: Pregabalin and gabapentin are effective in reducing postoperative pain following refractive surgeries, with pregabalin showing a greater effect. Both medications are safe, with no significant increase in adverse events. Further research with standardized methodologies and long-term follow-up is recommended to optimize postoperative pain management in ocular surgeries., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Topic: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) for management of pain in patients after photorefractive keratectomy (PRK)., Clinical Relevance: Pain after PRK is a major concern for both patients and surgeons. Although evidence supports the use of NSAIDs postoperatively, no consensus exists regarding the preferred regimen. The study aimed to compare the efficacy and safety of different topical NSAIDs., Methods: This study was prospectively registered with PROSPERO (ID: CRD42023417651). A systematic search of electronic databases was performed, for randomized controlled trials reporting topical NSAIDs' outcomes of corneal re-epithelization, rescue analgesics intake, and pain in days 0 to 3 after PRK (postoperative days [PODs] 0 to 3). Studies were graded for risk of bias. Data were extracted, and standardized mean differences (SMDs) were evaluated in a network meta-analysis in accordance with the Cochrane's guidelines, to which a frequentist approach model was fitted. Transitivity was assessed using the net split method. Treatment effectiveness was ranked using forest plots based on comparison with placebo. P-scores (P) and league tables were used to examine combined direct and indirect comparisons., Results: Of 1540 studies identified, 27 were included. These encompassed 2286 patients across 11 countries, evaluating 7 distinct topical NSAIDs. At POD0, ketorolac (P 0.764), flurbiprofen (P 0.763), and bromfenac (P 0.717) were the most efficient drugs overall and displayed significantly lower pain scores than placebo. Other than that, flurbiprofen held the highest rank for reported pain throughout, significantly outperforming placebo on POD1 (P 0.874, SMD -1.19, 95% CI -1.86 to -0.52), POD2 (P 0.882, SMD -1.05, 95% CI -1.82 to -0.27), and POD3 (P 0.939, SMD -1.14, 95% CI -2.1 to -0.18). Other NSAIDs were significantly better than placebo only on POD1 and POD0. Rescue analgesic intake analysis favored indomethacin (P 0.834, SMD -0.8, 95% CI -1.33 to -0.27), ketorolac, and diclofenac. Compared with placebo, re-epithelization was slowed to different significances with all NSAIDs but flurbiprofen (P 0.991, SMD -0.7, 95% CI -1.38 to -0.03)., Conclusions: Flurbiprofen was favorable in pain scores on typically painful postoperative days and re-epithelization times. However, analgesics intake, a more objective outcome, suggested superiority of other NSAIDs. Inconsistencies may be explained by the small sample size. For clinical interpretation, NSAID effect sizes should be taken into consideration., (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purpose: To compare topical nonsteroidal anti-inflammatory drug (NSAID) efficacy on intravitreal injection-induced pain reduction and determine the most efficient topical NSAID., Methods: This randomized-controlled study included 662 eyes of 662 patients. Based on the types of NSAID administered before intravitreal injection, eight subgroups were formed. In the control group, a sterile saline solution was applied instead of NSAIDs. The visual analog scale was used to assess pain scores after intravitreal injection. The visual analog scale scores were noted immediately and 6 hours following injection (sixth hour)., Results: Nepafenac 0.3%, nepafenac 0.1%, and bromfenac 0.09% had the lowest scores, immediately after and after 6 hours, with no significant differences. Diclofenac and ketorolac had higher visual analog scale scores than the first trio but lower scores than the control group. Flurbiprofen, pranoprofen, and indomethacin did not significantly affect immediate pain; however, at the sixth hour, the visual analog scale scores were significantly reduced., Conclusion: Nepafenac 0.3%, nepafenac 0.1%, and bromfenac 0.09% were the most effective NSAIDs for pain reduction. Although some NSAIDs did not have a significant effect on immediate pain, they all provided significant benefits at the sixth hour.

Purpose: To assess the therapeutic effect of tinted lenses (FL-41) on photophobia and light-evoked brain activity using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular surface pain., Design: Prospective case series., Methods: 25 subjects from the Miami veterans affairs (VA) eye clinic were recruited based on the presence of chronic ocular pain, dry eye symptoms, and photophobia. Using a 3T MRI scanner, subjects underwent 2 fMRI scans using an event-related design based on light stimuli: one scan while wearing FL-41 lenses and one without. Unpleasantness ratings evoked by the light stimuli were collected after each scan., Results: With FL-41 lenses, subjects reported decreased (n = 19), maintained (n = 2), or increased (n = 4) light-evoked unpleasantness ratings. Group analysis at baseline (no lens) revealed significant light evoked responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral insula, bilateral frontal pole, visual, precuneus, paracingulate, and anterior cingulate cortices (ACC) as well as cerebellar vermis, bilateral cerebellar hemispheric lobule VI, and bilateral cerebellar crus I and II. With FL-41 lenses, light-evoked responses were significantly decreased in bilateral S1, bilateral S2, bilateral insular, right temporal pole, precuneus, ACC, and paracingulate cortices as well as bilateral cerebellar hemispheric lobule VI., Conclusion: FL-41 lenses modulated photophobia symptoms in some individuals with chronic ocular pain. In conjunction, FL-41 lenses decreased activation in cortical areas involved in processing affective and sensory-discriminative dimensions of pain. Further research into these relationships will advance the ability to provide precision therapy for individuals with ocular pain., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The management of post-refractive surgery dry eye disease (DED) can be challenging in clinical practice, and patients usually show an incomplete response to traditional artificial tears, especially when it is complicated with ocular pain. Therefore, we aim to investigate the efficacy of combined topical 0.05% cyclosporine A and 0.1% sodium hyaluronate treatment in post-refractive surgery DED patients with ocular pain unresponsive to traditional artificial tears., Methods: We enrolled 30 patients with post-refractive surgery DED with ocular pain who were unresponsive to traditional artificial tears. Topical 0.05% cyclosporine A and 0.1% sodium hyaluronate were used for 3 months. They were evaluated at baseline and 1 and 3 months for dry eye and ocular pain symptoms and objective parameters, including Numerical Rating Scale (NRS), Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-Eye), tear break-up time (TBUT), Schirmer I test (SIt), corneal fluorescein staining (CFS), corneal sensitivity, and corneal nerve morphology. In addition, tear levels of inflammatory cytokines and neuropeptides were measured using the Luminex assay., Results: After 3 months of treatment, patients showed a statistically significant improvement in the ocular surface disease index (OSDI), TBUT, SIt, CFS, and corneal sensitivity (all P < 0.01) using linear mixed models. As for ocular pain parameters, the NRS and NPSI-Eye scores were significantly reduced (both P < 0.05) and positively correlated with the OSDI and CFS scores. Additionally, tear IL-1β, IL-6, and TNF-α levels were improved better than pre-treatment (P = 0.01, 0.03, 0.02, respectively)., Conclusion: In patients with post-refractive surgery DED with ocular pain, combined topical 0.05% cyclosporine A and 0.1% sodium hyaluronate treatment improved tear film stability, dry eye discomfort, and ocular pain, effectively controlling ocular inflammation., Trial Registration: Registration number: NCT06043908., (© 2024. The Author(s).)

Purpose: Patients with dry eye disease (DED) sometimes complain of ocular pain. DED-related ocular pain has many similarities with neuropathic pain. Mirogabalin, a novel ligand for the α2δ subunit of voltage-gated calcium channels, is approved for treating neuropathic pain in Japan. This study aimed to investigate the effect of mirogabalin on hyperalgesia and chronic ocular pain in a rat DED model., Methods: DED was induced in female Sprague Dawley rats by unilaterally excising the external lacrimal gland (ELG) and Harderian gland (HG). After 4 weeks of ELG and HG removal, tear production (pH threads) and corneal epithelial damage (fluorescein staining) were evaluated. Corneal hyperalgesia and chronic pain were analyzed, respectively, by measuring capsaicin-induced eye-wiping behavior and c-Fos expression in the trigeminal nucleus. Mirogabalin (10 or 3 mg/kg) was evaluated for effects on DED-induced hyperalgesia and chronic ocular pain., Results: Tear production was significantly lower in DED-induced eyes than in control eyes. Corneal damage was significantly higher in DED eyes than in control eyes. Hyperalgesia and chronic ocular pain were detected 4 weeks after ELG and HG removal. Five days of mirogabalin administration significantly suppressed capsaicin-induced eye-wiping behavior, which indicated the suppression of ocular hyperalgesia. Administration of 10 mg/kg mirogabalin significantly reduced c-Fos expression in the trigeminal nucleus, which indicated the amelioration of chronic ocular pain., Conclusions: Mirogabalin suppressed DED-induced hyperalgesia and chronic ocular pain in a rat DED model. Our findings suggested that mirogabalin might effectively alleviate chronic ocular pain in patients with DED.

Abstract: Several etiologies can contribute to ocular surface pain including nociceptive, peripheral neuropathic, and central neuropathic mechanisms. Clinical clues can help identify contributors to ocular surface pain in a patient. In individuals whose pain persists despite targeting nociceptive contributors, neuropathic mechanisms should be considered and addressed using oral, topical, and/or adjuvant agents., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The goal of this study was to examine the temporal relationship of eye pain to visual loss and investigate whether timing of steroid treatment affects the rate and extent of visual recovery in optic neuritis (ON) from MOG-IgG associated disease (MOGAD) in a large cohort of MOGAD patients with ON., Methods: This is a multicenter, retrospective cohort study of consecutive MOGAD patients with ON attacks seen from 2017 to 2021 fulfilling the following criteria: (1) clinical history of ON; (2) MOG-IgG seropositivity. ON attacks were evaluated for presence/duration of eye pain, nadir of vision loss, time to intravenous methylprednisolone (IVMP) treatment, time to recovery, and final visual outcomes., Results: There were 107 patients with 140 attacks treated with IVMP and details on timing of treatment and outcomes. Eye pain was present in 125/140 (89%) attacks with pain onset a median of 3 days (range, 0 to 20) prior to vision loss. Among 46 ON attacks treated with IVMP within 2 days of onset of vision loss, median time to recovery was 4 days (range, 0 to 103) compared to 15 days (range, 0 to 365) in 94 ON attacks treated after 2 days (p = 0.004). Those treated within 2 days had less severe VA loss at time of treatment (median LogMAR VA 0.48, range, 0.1 to 3) compared to those treated after 2 days (median LogMAR VA 1.7, range, 0 to 3; p < 0.001), and were more likely to have a VA outcome of 20/40 or better (98% vs 83%, p = 0.01). After adjustment for the initial VA at time of treatment, the differences in final VA were no longer significantly different (p = 0.14). In addition, some patients were documented to recover without steroid treatment., Conclusion: This study suggests that pain precedes vision loss in the majority of ON attacks and early steroids may lead to better outcomes in MOG-IgG ON, but some patients can recover without steroid treatment. Prospective randomized clinical trials are required to confirm these findings., Competing Interests: Declaration of Competing Interests None., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: The purpose of this study was to characterize rates of opioid prescription for different ulcerative keratitis types., Methods: This cohort study included patients diagnosed with ulcerative keratitis according to the University of Michigan electronic health record data between September 1, 2014 and December 22, 2020. Ulcerative keratitis was categorized by etiologic type (bacterial, fungal, viral, acanthamoeba, inflammatory, polymicrobial, or unspecified) using rule-based data classification that accounted for billing diagnosis code, antimicrobial or antiinflammatory medications prescribed, laboratory results, and manual chart review. Opioid prescriptions were converted to morphine milligram equivalent and summed over 90 days from diagnosis. Opioid prescription rate and amount were compared between ulcerative keratitis types., Results: Of 3322 patients with ulcerative keratitis, 173 (5.2%) were prescribed at least 1 opioid for pain management within 90 days of diagnosis. More patients with acanthamoeba (32.4%), fungal (21.1%), and polymicrobial (25.0%) keratitis were treated with opioids compared with bacterial (6.7%), unspecified (2.9%), or viral (1.8%) keratitis (all Bonferroni adjusted P < 0.05). For the 173 patients who were prescribed opioids, a total of 353 prescriptions were given within 90 days of diagnosis, with half given within the first week after diagnosis. The quantity of opioid prescribed within 90 days from diagnosis was not significantly different between ulcerative keratitis types (P = 0.6559). Morphine milligram equivalent units prescribed ranged from 97.5 for acanthamoeba keratitis to 112.5 for fungal keratitis., Conclusions: The type of ulcerative keratitis may influence the opioid prescription rate. Providers can better serve patients needing opioids for pain management through improved characterization of pain and development of more tailored pain management regimens., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Purpose of the present systematic review is to investigate preclinical evidence in favor of the working hypothesis of efficacy of cannabinoids in ocular pain treatment., Methods: Literature search includes the most relevant repositories for medical scientific literature from inception until November, 24 2021. Data collection and selection of retrieved records adhere to PRISMA criteria., Results: In agreement with a priori established protocol the search retrieved 2471 records leaving 479 results after duplicates removal. Eleven records result from title and abstract screening to meet the inclusion criteria; only 4 results are eligible for inclusion in the qualitative synthesis impeding meta-analysis. The qualitative analysis highlights the antinociceptive and anti-inflammatory efficacy of Δ8-tetrahydrocannabinol, cannabidiol and its derivative HU-308 and of new racemic CB1 allosteric ligand GAT211 and its enantiomers GAT228 and GAT229. Moreover, CB2R agonists RO6871304 and RO6871085 and CB2R ligand HU910 provide evidence of anti-inflammatory efficacy. CB2 agonist HU308 reduces of 241% uveitis-induced leukocyte adhesion and changes lipidome profile. Methodological and design issues raise concern of risk of bias and the amount of studies is too small for generalization. Furthermore, the ocular pain model used can resemble only inflammatory but not neuropathic pain., Conclusions: The role of the endocannabinoid system in ocular pain is underinvestigated, since only two studies assessing the effects of cannabinoid receptors modulators on pain behavior and other two on pain-related inflammatory processes are found. Preclinical studies investigating the efficacy of cannabinoids in ocular inflammatory and neuropathic pain models are needed to pave the way for clinical translation., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: Dry eye-induced chronic ocular pain is also called ocular neuropathic pain. However, details of the pathogenic mechanism remain unknown. The purpose of this study was to elucidate the pathogenic mechanism of dry eye-induced chronic pain in the anterior eye area and develop a pathophysiology-based therapeutic strategy., Methods: We used a rat dry eye model with lacrimal gland excision (LGE) to elucidate the pathogenic mechanism of ocular neuropathic pain. Corneal epithelial damage, hypersensitivity, and hyperalgesia were evaluated on the LGE side and compared with the sham surgery side. We analyzed neuronal activity, microglial and astrocytic activity, α2δ-1 subunit expression, and inhibitory interneurons in the trigeminal nucleus. We also evaluated the therapeutic effects of ophthalmic treatment and chronic pregabalin administration on dry eye-induced ocular neuropathic pain., Results: Dry eye caused hypersensitivity and hyperalgesia on the LGE side. In the trigeminal nucleus of the LGE side, neuronal hyperactivation, transient activation of microglia, persistent activation of astrocytes, α2δ-1 subunit upregulation, and reduced numbers of inhibitory interneurons were observed. Ophthalmic treatment alone did not improve hyperalgesia. In contrast, continuous treatment with pregabalin effectively ameliorated hypersensitivity and hyperalgesia and normalized neural activity, α2δ-1 subunit upregulation, and astrocyte activation., Conclusions: These results suggest that dry eye-induced hypersensitivity and hyperalgesia are caused by central sensitization in the trigeminal nucleus with upregulation of the α2δ-1 subunit. Here, we showed that pregabalin is effective for treating dry eye-induced ocular neuropathic pain even after chronic pain has been established.

Purpose : While cannabis has the potential to reduce corneal pain, cannabinoids might induce side effects. This review article examines the effects of cannabinoids on the cornea. As more states and countries consider the legalization of adult cannabis use, health-care providers will need to identify ocular effects of cannabis consumption. Methods : Studies included in this review examined the connection between cannabis and the cornea, more specifically anti-nociceptive and anti-inflammatory actions of cannabinoids. NCBI Databases from 1781 up to December 2019 were consulted. Results : Five studies examined corneal dysfunctions caused by cannabis consumption (opacification, decreased endothelial cell density). Twelve studies observed a reduction in corneal pain and inflammation (less lymphocytes, decreased corneal neovascularization, increased cell proliferation and migration). Conclusion : More than half of the studies examined the therapeutic effects of cannabinoids on the cornea. As the field is still young, more studies should be conducted to develop safe cannabinoid treatments for corneal diseases.

Purpose: A consecutive case series of patients with dupilumab-associated ocular surface disease (DAOSD) that describes common ocular symptoms and signs, proposes a symptom disease severity grading system, and describes treatment strategies of DAOSD patients was evaluated., Methods: A retrospective chart review of patients with concomitant dupilumab-treated atopic dermatitis and DAOSD with ophthalmic evaluation between January 2014 and May 2019 was conducted., Results: Twenty-nine patients (mean age 46 years, M/F: 12/17) with 57 ophthalmic exams were identified. The most common ocular symptoms included irritation/pain (n = 28, 97%), redness (n = 24, 83%), pruritus (n = 18, 62%), discharge (n = 18, 62%), and light sensitivity (n = 6, 21%). The most frequent signs included conjunctival injection (n = 18, 62%), superficial punctate keratitis (n = 16, 55%), and papillary reaction (n = 8, 28%). Topical corticosteroids (TCS) (n = 23, 79%), tacrolimus (n = 6, 21%), and artificial tears (n = 7, 24%) were the most commonly used therapies. Of those with follow-up documentation (n = 21), 20 were noted to have partial or complete response with TCS based on symptoms and reduction of signs. Using our proposed symptom-based grading scale, scaled 1 to 5 based on the presence of common symptoms listed above, 66% (n = 19) requiring topical immunomodulating therapy were found in the 'severe' group (≥3 symptoms) and 17% (n = 5) were found in the 'mild' group (≤2 symptoms)., Conclusions: This study provides insight into the commonly presenting ocular signs and symptoms associated with DAOSD and highlights the efficacy of TCS and other immunomodulators in improving symptoms associated with DAOSD. Based on our findings, we propose a symptom-based grading system that can guide nonophthalmic physicians regarding ophthalmology consult., Competing Interests: Eric Simpson is a consultant and investigator for Regeneron and Sanofi. The remaining authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The number of opioid-related overdose deaths has rapidly increased since 2000, increasing more than five-fold from 1999 to 2016. Although surgeons only write 10% of opioid prescriptions annually, with ophthalmologists writing only a fraction of this amount, all physicians need to be cognizant of the current opioid epidemic and ways to decrease unnecessary opioid prescriptions., Recent Findings: Previous work within ophthalmology has shown that retrobulbar anesthesia along with peri-operative intravenous or oral nonopioid analgesics can lead to decreased postoperative opioid use following ophthalmic surgery. Recent literature has shifted focus towards the use of opioid prescription guidelines in managing postoperative pain and decreasing the number of unnecessary opioids being prescribed by ophthalmologists. Overall, the frequency of opioid prescriptions may have gradually declined the past few years with such efforts, increased awareness, and new healthcare policies to monitor opioid prescriptions. However, ophthalmologists still continue to prescribe a substantial number of opioid medications, much of which may not be necessary., Summary: This review serves as a tool to aid all ophthalmologists in managing postoperative pain. There is a recent trend in addressing the opioid epidemic and efforts are being made to limit the overprescribing of opioids. Continued efforts are still required by all ophthalmologists to address the current opioid epidemic., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This study aims to evaluate the efficacy of gabapentin treatment in dry eye disease (DED) and neuropathic ocular pain. Our study was performed with 72 patients. The painDETECT questionnaire was used for neuropathic pain screening. Patients who were thought to have severe DED according to ocular surface disease index (OSDI) questionnaire, Schirmer's test type 1 and tear break up time test results were treated with artificial tear and cyclosporine drops. Gabapentin treatment was also initiated in addition to artificial tear and cyclosporine drops treatments to the patients with neuropathic component and DED findings. We divided the patients into two groups: group 1 (n: 36), patients treated with artificial tear and cyclosporine drops and group 2 (n: 36), patients treated with artificial tear, cyclosporine drops and gabapentin. In the first evaluation, no significant differences were found between groups in terms of OSDI score, Schirmer's test result and TBUT. After the 6 weeks of treatment, in both groups OSDI score, Schirmer's test result and TBUT statistically significantly improved. OSDI score, Schirmer's test result and TBUT significantly improved after the 6 weeks of gabapentin treatment than artificial tear and cyclosporine treatment group (p < 0.001). Dry eye patients should be screened for neuropathic ocular pain symptoms and individualized treatment has to be applied. Our study showed that the use of gabapentin is effective in severe dry eye patients with neuropathic ocular pain.

Study Objective: The objective of this study is to show that patients with corneal abrasions would experience more pain relief with short-term topical tetracaine than placebo., Methods: The study was a prospective, double-blind, randomized trial of tetracaine versus placebo set in the emergency department (ED). A total of 118 adults who presented with uncomplicated corneal abrasions were included and randomized. The intervention was either topical tetracaine or placebo applied every 30 minutes as needed for 24 hours. The primary outcome was the overall numeric rating scale pain score measured at the 24- to 48-hour ED follow-up examination., Results: One hundred eleven patients were included in the final analysis, 56 in the tetracaine group and 55 in the placebo group. At the 24- to 48-hour follow-up, the overall numeric rating scale pain score after use of the study drops was significantly lower in the tetracaine group (1) versus placebo group (8) (Δ7; 95% confidence interval 6 to 8). Patients in the tetracaine group used less hydrocodone than those in the placebo group. The complication rates between the 2 groups were similar., Conclusion: Short-term topical tetracaine is an efficacious analgesic for acute corneal abrasions, is associated with less hydrocodone use compared with placebo, and was found to be safe in this sample., (Copyright © 2020. Published by Elsevier Inc.)

Corneal pain is considered to be a core symptom of ocular surface disruption and inflammation. The management of this debilitating condition is still a therapeutic challenge. Recent evidence supports a role of the opioid system in the management of corneal nociception. However, the functional involvement of the mu opioid receptor (MOR) underlying this analgesic effect is not known. We first investigated the expression of the MOR in corneal nerve fibers and trigeminal ganglion (TG) neurons in control mice and a mouse model of corneal inflammatory pain. We then evaluated the anti-nociceptive and electrophysiological effects of DAMGO ([D-Ala 2 ,N-Me-Phe 4 ,Gly 5 -ol] enkephalin), a MOR-selective ligand. MOR immunoreactivity was detected in corneal nerve fibers and primary afferent neurons of the ophthalmic branch of the TG of naive mice. MOR expression was significantly higher in both structures under conditions of inflammatory corneal pain. Topical ocular administration of DAMGO strongly reduced both the mechanical (von Frey) and chemical (capsaicin) corneal hypersensitivity associated with inflammatory ocular pain. Repeated instillations of DAMGO also markedly reversed the elevated spontaneous activity of the ciliary nerve and responsiveness of corneal polymodal nociceptors that were observed in mice with corneal pain. Finally, these DAMGO-induced behavioral and electrophysiological responses were totally blunted by the topical application of naloxone methiodide, an opioid receptor antagonist. Overall, these results provide evidence that topical pharmacological MOR activation may constitute a therapeutic target for the treatment of corneal pain and improve corneal nerve function to alleviate chronic pain., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Competing Interests: Competing interests: None declared.

Purpose: Neuropathic corneal pain (NCP) is a recently acknowledged disease entity. However, there is no consensus in potential treatment strategies, particularly in patients with a centralized component of pain. This study aims to assess the efficacy and tolerability of the tricyclic antidepressant, nortriptyline, among NCP patients., Methods: Patients with clinically diagnosed NCP and a centralized component of pain, treated with oral nortriptyline, who had recorded pain scores as assessed by the ocular pain assessment survey at the first and last visit were included. Patients were excluded if they had any other ocular pathology that might result in pain or had less than 4 weeks of nortriptyline use. Demographics, time between visits, concomitant medications, systemic and ocular co-morbidities, duration of NCP, side effects, ocular pain scores, and quality of life (QoL) assessment were recorded., Results: Thirty patients with a mean age of 53.1 ± 18.5 were included. Male to female ratio was 8:22. Mean ocular pain in the past 24 h improved from 5.7 ± 2.1 to 3.6 ± 2.1 after 10.5 ± 9.1 months (p < 0.0001). Twelve patients (40.0%) had equal to or more than 50% improvement, 6 patients (20.0%) had 30-49% improvement, 6 patients (20.0%) had 1-29% improvement, 4 patients (13.3%) did not improve, while 2 patients (6.7%) reported increase in pain levels. Mean QoL improved from 6.0 ± 2.5 to 4.3 ± 2.4 (p = 0.019). Eight patients (26.6%) discontinued treatment due to persistent side effects, despite improvement by 22.4%., Conclusion: Nortriptyline was effective in relieving NCP symptoms in patients with centralized component and insufficient response to other systemic and topical therapies who tolerated the drug for at least 4 weeks. Nortriptyline may be used in the management of patients with NCP., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

This paper has two main purposes: (1) to report a rare case of paediatric gliosarcoma that invaded the surrounding orbit and (2) to demonstrate chlorpromazine injection as a potential treatment option for blind, painful eye caused by tumour invasion. A 12-year-old man who presented with headaches was found to have glioblastoma multiforme and it was excised and treated with radiation and chemotherapy. Seven months later, the tumour recurred as gliosarcoma, a rare variant of glioblastoma multiforme containing distinct gliomatous and sarcomatous components. In spite of treatment, the tumour progressed and eventually invaded into the right orbit. He subsequently developed a proptotic, blind, painful eye and was treated with retrobulbar chlorpromazine injection, which provided immediate symptomatic relief., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Topic: The role of topical nonsteroidal anti-inflammatory drugs (NSAIDs) for the reduction of ocular pain after intravitreal injections (IVIs) has been explored. To provide clarity on the evidence for these agents, the present meta-analysis of randomized controlled trials (RCTs) was undertaken., Clinical Relevance: No standard of care regimen exists for the management of pain resulting from IVIs., Methods: A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central from inception through July 2019. The RCTs that treated patients with a topical NSAID and assessed postprocedural pain were included. Risk of bias was assessed using the Cochrane guidelines. For all analyses, weighted mean differences (WMDs) with 95% confidence intervals (CIs) were reported. Random effects models were used for all analyses. The primary analysis analyzed pain on a 0- to 10-point visual analog scale. Literature estimates were categorized into the following postprocedure time point groups: 1 hour or less, 1 to 24 hours (although data were available only at 6 hours), and 24 hours or more. A subgroup analysis stratified studies based on agent and preprocedure versus postprocedure administration., Results: From 241 results, 9 RCTs and 598 eyes were included. A low to medium risk of bias was found across the included studies. The mean pain score on a 0-to-10 visual analog scale was significantly lower after topical NSAID administration relative to control at 1 hour or less after IVI (WMD, -1.01 units; 95% CI, -1.38 to -0.65; P < 0.001), 6 hours after IVI (WMD, -2.17 units; 95% CI, -2.67 to -1.68; P < 0.001; threshold met for clinical significance, defined as WMD >1.2 units), and more than 24 hours after IVI (WMD, -0.75 units; 95% CI, -1.11 to -0.38; P < 0.001). A greater effect size was seen with administration of NSAIDs before versus after IVI, as well as topical nepafenac relative to ketorolac or diclofenac., Discussion: At 6 hours after the procedure, NSAIDs provide a clinically meaningful reduction in pain relative to a control group. The administration of NSAIDs before the procedure, specifically topical nepafenac, was associated with the greatest improvement in pain relative to the control group., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: There is a recognition that nerve dysfunction can contribute to chronic ocular pain in some individuals. However, limited data are available on how to treat individuals with a presumed neuropathic component to their ocular pain. As such, the purpose of this study was to examine the efficacy of our treatment approaches to this entity., Methods: A retrospective review of treatments and outcomes in individuals with chronic ocular pain that failed traditional therapies., Results: We started eight patients on an oral gabapentinoid (gabapentin and/or pregabalin) as part of their pain regimen (mean age 46 years, 50% women). Two individuals reported complete ocular pain relief with a gabapentinoid, in conjunction with their topical and oral medication regimen. Three individuals noted significant improvements, one slight improvement, and two others no improvement in ocular pain with gabapentin or pregabalin. We performed periocular nerve blocks (4 mL of 0.5% bupivacaine mixed with 1 mL of 80 mg/mL methylprednisolone acetate) targeting the periocular nerves (supraorbital, supratrochlear, infratrochlear, and infraorbital) in 11 individuals (mean age 54 years, 36% women), 10 of whom had previously used a gabapentinoid without ocular pain improvement. Seven individuals experienced pain relief after nerve blocks that lasted from hours to months and four failed to benefit. Five of the individuals who experienced pain relief underwent repeat nerve blocks, weeks to months later., Conclusions: Approaches used to treat chronic pain outside the eye can be applied to ocular pain that is not responsive to traditional therapies.

Despite being a common presenting symptom to eye-care clinics, many ophthalmologists have difficulty diagnosing and managing ocular surface pain. The purpose of this review is to discuss potential causes of ocular surface pain, focusing on both nociceptive and neuropathic aetiologies. Specifically, we outline an approach to the diagnosis of ocular surface pain and focus on various management strategies, providing supporting evidence on the efficacy of various treatments.

Ocular involvement in leukemia is considered rare. Ocular symptoms can be the presenting signs of leukemia, they can appear after diagnosis has been established, or they can be the first manifestation of a relapse after remission. We report, to the best of our knowledge for the first time, the ocular manifestation of a series of patients with ocular leukemia and the result of their treatment with intravitreal methotrexate (MTX) injections. This is a retrospective cohort study. The medical records of 12 consecutive patients with ocular leukemia (24 eyes, 11 eyes treated with MTX) treated at the Sheba Medical Center from January 2010 to December 2017 were retrospectively reviewed. Details on ocular inflammatory reaction and tumor cell infiltration at presentation and the end of follow-up were recorded as main outcome measures. The 12 patients included 7 women and 5 men (mean age ± standard deviation at diagnosis 25.92 ± 23.91 years, range 2-82 years). Eleven eyes of 6 patients were treated with intravitreal MTX injections. The indication for treatment was biopsy proven, tumor cell infiltration. The mean number of MTX injections was 3.37 ± 5.35 (range 1-18). The mean follow-up was 27.08 ± 36.79 months (range 1-93). All treated eyes showed improvement in the inflammatory reaction and tumor cell infiltration. In conclusion we found that Intravitreal MTX injections may be an effective therapeutic approach for eyes with intraocular leukemic tumor cell infiltration.

Importance: Opioids, which carry a high risk for addiction and overdose, are commonly prescribed after corneal surgery. Data are lacking describing opioid prescribing practices and opioid needs by patients after ophthalmic surgery., Objectives: To quantify opioid use and to assess the association of decreasing the number of opioid tablets prescribed after corneal surgery with postsurgical use., Design, Setting, and Participants: This prospective cohort study investigated opioid use after corneal surgery using direct interviews of 2 adult patient cohorts separated by an updated opioid prescribing guideline. The first cohort survey assessed the quantity of opioid tablets used after surgery. The cornea division of a tertiary care academic medical center reviewed the use needs and decreased the number of tablets prescribed after routine cases. Simultaneously, a statewide opioid monitoring program began that provided patients with opioid information. A second unique cohort received a more detailed survey to assess use, opioid disposal, and pain control. Data for the first cohort were collected from December 1, 2017, through January 19, 2018; for the second cohort, from June 1 to September 15, 2018. Data were analyzed from October 24, 2018, through September 24, 2019., Exposure: Corneal surgery., Main Outcomes and Measures: Differences in use of opioid tablets used by both patient cohorts, assessed using the 2-sample t test., Results: Of 112 eligible, contacted patients, 82 consented to participate (42 men [51%]; mean [SD] age, 42.5 [17.8] years) and were included in the analysis; 38 of 42 participated in the first cohort and 44 of 70 participated in the second cohort. Of those receiving opioid prescriptions, the first cohort was prescribed significantly more tablets than the second cohort (mean [SD], 18.8 [4.2] vs 6.6 [3.1]; difference, 12.2 [95% CI, 10.4-14.0]; P < .001). The first cohort used significantly more tablets than the second cohort (mean [SD], 8.3 [7.0] vs 4.0 [3.2]; difference, 4.3 [95% CI, 1.4-7.2]; P = .005) and had significantly more leftover tablets (mean [SD], 10.3 [6.9] vs 2.9 [2.7]; difference, 7.5 [95% CI, 4.7-10.2]; P < .001). In the detailed survey for the second cohort, 19 of 27 patients reported pain control as adequate (70% [95% CI, 50%-86%]); 6 of 27, as more than needed (22% [95% CI, 9%-42%]). Twenty of 28 participants (71% [95% CI, 55%-88%]) had leftover tablets; 17 of these (85% [95% CI, 62%-97%]) did not dispose of leftovers, and 3 (15% [95% CI, 3%-38%]) threw away or flushed leftovers., Conclusions and Relevance: After an assessment of opioid needs, physicians prescribed fewer opioid pills. However, patients who underwent cornea surgery and received fewer tablets continued to have adequate pain control and used even fewer tablets compared with the initial cohort. Patients with unused opioid tablets did not dispose of them properly.

Pembrolizumab is a programmed cell death protein 1 (PD-1) monoclonal antibody used in the treatment of metastatic melanomas. Severe ocular complications appear in less than 1% of the patients and require early treatment. We present the case of a patient diagnosed with a BRAF mutated metastatic melanoma. Ocular pain and a blurred vision appeared after treatment and the patient visited the ophthalmology emergency room, where he was diagnosed with acute anterior uveitis (AAU), synechiae, and bilateral papillitis. The patient was treated with topical corticosteroids, prednisone, and mydriatics, which immediately improved the patient's status. Therefore, when an ocular inflammatory disease exists, immune checkpoint inhibitor treatments must be ruled out as possible causes., Competing Interests: None

Purpose: Pain after an intravitreal injection (IVI) can last up to 7 days and negatively impacts the patient's experience, potentially reducing treatment compliance. We prospectively evaluated topical nepafenac 0.3% suspension and patching for the reduction of pain after IVI., Design: Randomized controlled trial., Participants: Sixty patients receiving an IVI of bevacizumab, aflibercept, or triamcinolone acetonide in 1 eye., Methods: Participants were randomized equally to receive either a single drop of nepafenac 0.3%, a pressure patch for 2 hours, or a single drop of preservative-free artificial tears (control group). A single-blinded placebo-controlled design was used to mask the topical treatment used. Pain was assessed using the Numeric Pain Rating Scale that ranged from 0 to 10 (horizontal pain scale). Because pain scores were not normally distributed, statistical analysis was performed using a nonparametric randomization-based analysis of covariance., Main Outcome Measure: Pain scores., Results: Fifty-six and 53 patients of the 60 patients enrolled completed the 6- and 24-hour follow-ups, respectively. Numeric Pain Rating Scale scores at 6 and 24 hours after IVI were lower in the nepafenac group (0.8±0.3 and 0.1±0.1, respectively; n = 18) and the patching group (1.3±0.4 and 0.4±0.2, respectively; n = 19) compared with the control group (2.5±0.6 and 0.9±0.4, respectively; n = 19). After controlling for age, gender, number of prior injections, and physician administering the injection, patients in the nepafenac group reported significantly lower pain scores than those in the control group at 6 hours (1.3±0.6 less; P = 0.047) and 24 hours (0.7±0.3 less; P = 0.047). Although the patching group reported lower pain scores than the control group, this was not statistically significant (6 hours, P = 0.24; 24 hours, P = 0.29)., Conclusions: Nepafenac 0.3% was effective as a single drop in reducing pain at 6 and 24 hours after IVI compared with placebo. Limited patching was associated with lower pain scores than placebo, but the difference was not statistically significant. Additional studies are needed to determine the most effective method to maximize the patient's experience after an IVI without sacrificing outcomes., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report the clinical features and outcomes of toxic keratitis after application of powdered custard apple seeds for hair washing for head lice infestation., Methods: Retrospective review of all patients with toxic keratitis after application of powdered custard apple seed for head lice infestation during the time period from January 2015 to December 2017. Demographic details, clinical features, and visual outcomes were documented., Results: Thirty-one eyes of 19 patients with toxic keratitis after application of crushed custard apple seeds for head lice infestation were included in the study. Eighteen females and 1 male with a median age of 14 years [interquartile range (IQR) 12-34 years] presented with severe epiphora, congestion, photophobia, and defective vision (median logMar visual acuity 0.4, IQR 0.2-0.8) after application of custard apple seed powder for hair washing. Ten eyes (32.2%) had an epithelial defect (median size 9 mm, IQR 5-12 mm), and 21 (67.7%) eyes had punctate epithelial erosions. All the patients were treated with topical antibiotics, and at 3 days follow-up, all of them had resolution of symptoms and signs with a median logarithm of the minimum angle of resolution (logMAR) visual acuity of 0 (IQR 0-0.2)., Conclusions: Health education about the harmful effect of this traditional practice for head lice infestation will prevent further similar events.

Purpose: Patients undergoing primary pterygium excision with autologous conjunctival autograft and human tissue adhesive in New Zealand, currently receive subconjunctival anesthesia with oral postoperative analgesia for pain. Our aim was to investigate the potential added benefit of intraoperative subtenon bupivacaine to this regimen., Methods: A double-blinded, placebo-controlled, randomized trial was conducted at 2 centers. All patients received topical and subconjunctival anesthesia intraoperatively, with standardized oral analgesia as required postoperatively. Participants were allocated to receive subtenon bupivacaine 0.5% or placebo at the conclusion of surgery. Corneal epithelial defect and conjunctival graft size were recorded. Pain and ocular surface irritation were assessed (Likert scale) immediately postoperatively at 3, 6, 12, 24, and 36 hours. Cumulative oral analgesia consumption (doses) was reported at 24 and 36 hours., Results: Forty-two patients were randomized with participants evenly matched at baseline. Postoperative pain at all time points ≤24 hours was significantly less (2.4 vs. 1.2; P < 0.04) in the bupivacaine arm with no difference at 36 hours (P = 0.27). Ocular surface irritation was also significantly less at all time points ≤12 hours (4.8 vs. 1.3; P < 0.01) with no difference at 24 hours (P = 0.10). Analgesia consumption was less in the bupivacaine arm at 24 (6.5 vs. 2.5; P < 0.01) and 36 hours (7.6 vs. 3.4; P < 0.01). No complications were observed., Conclusions: Intraoperative subtenon bupivacaine improves patient comfort after pterygium excision by reducing pain, irritation, and requirement for oral analgesia after surgery.

Purpose: To describe a patient with chronic periocular pain after bilateral photorefractive keratectomy (PRK) and ocular neuralgia that was controlled with regular orbital steroid and anesthetic injections., Methods: Case report., Results: A 21-year-old man presented 3 months following bilateral PRK surgery in severe bilateral orbital pain. Previous treatments included topical (artificial tears, corticosteroids, and nonsteroidal anti-inflammatory drugs [NSAIDs) and oral (NSAIDs, opioids, and pregabalin) therapies with minimal pain relief. A bilateral orbital triamcinolone acetonide 40 mg/cc and 0.25% bupivacaine injection was done after a successful, diagnostic unilateral 0.25% bupivacaine injection. Following bilateral bupivacaine and triamcinolone acetonide injections, pain intensity improved from 7 of 9 to 1 of 3 out of 10. Repeat injections have been regularly performed over the past 3 years, allowing the patient to experience improved symptoms lasting from 4 to 9 months., Conclusions: In this case, orbital nerve blocks provided relief and may be considered as a potential treatment for orbital neuralgia after refractive surgery. [J Refract Surg. 2019;35(8):534-537.]., (Copyright 2019, SLACK Incorporated.)

Topical ophthalmic corticosteroids are of clinical benefit in the management of pain and inflammation after ocular surgery; however, their use can be associated with class-associated adverse events (AEs) and limited bioavailability. Selection of an appropriate topical corticosteroid depends on drug-specific variables such as AE profile, efficacy, potency, dosing, patient-specific administration needs, and formulation properties aimed at minimizing precorneal drug loss, increasing ocular surface drug residence time, and maximizing drug delivery to the anterior tissues. Recently, strategies for improving ocular penetration of ophthalmic formulations have included use of mucoadhesive formulations (ie, polycarbophil-containing gels) and drug particle size reduction, enabling faster drug dissolution and therefore increased bioavailability and penetration. Loteprednol etabonate (LE) is a carbon-20 ester corticosteroid developed through retrometabolic drug design with potent anti-inflammatory effects and a reduced propensity for eliciting corticosteroid class AEs. This drug has been formulated for topical ophthalmic use after surgery as 0.5% and 1% suspensions, a 0.5% ointment, and a 0.5% gel. Preclinical and clinical data for a new 0.38% LE gel will be reviewed demonstrating that reducing the drug particle size to the nanometer range in diameter provides effective ocular tissue penetration and resolution of pain and inflammation despite a reduced drug concentration (0.38%) and dosing frequency.

Fucoxanthin is a carotenoid with many pharmaceutical properties that is found in brown seaweed. However, the effects of fucoxanthin on corneal innervation and intense eye pain have not been extensively examined. To clarify the protective roles and underlying mechanisms of fucoxanthin on ocular lesions, we investigated the beneficial effects and mechanisms by which fucoxanthin ameliorates ultraviolet B (UVB)-induced corneal denervation and trigeminal pain. Treatment with fucoxanthin enhanced the expression of nuclear factor erythroid 2-related factor 2 in the cornea. Inhibition of typical denervation and epithelial exfoliation in the cornea were observed in rats treated with fucoxanthin following UVB-induced nerve disorders. Moreover, the active phosphorylated form of p38 MAP kinase (pp38) and the number of glial fibrillary acidic protein (GFAP)-positive neural cells were significantly reduced. Decreased expression of neuron-selective transient receptor potential vanilloid type 1 (TRPV1) in the trigeminal ganglia neurons was also demonstrated in rats treated with fucoxanthin after UVB-induced keratitis. Symptoms of inflammatory pain, including difficulty in opening the eyes and eye wipe behaviour, were also reduced in fucoxanthin-treated groups. Pre-treatment with fucoxanthin may protect the eyes from denervation and inhibit trigeminal pain in UVB-induced photokeratitis models.

Purpose: To assess the efficacy and safety of a sustained-release intracanalicular dexamethasone insert for the treatment of postoperative ocular inflammation and pain in patients having cataract surgery., Setting: Twenty-one United States sites., Design: Prospective multicenter randomized parallel-arm double-masked vehicle-controlled phase 3 study., Methods: Patients with planned clear corneal cataract surgery were randomized (1:1) to receive dexamethasone insert or placebo, and the treatment was placed in the canaliculus of the eye immediately after surgery (Day 1). The primary efficacy endpoints were complete absence of anterior chamber cells at Day 14 and complete absence of pain at Day 8., Results: The study comprised 438 adult patients (216 in the treatment arm and 222 in the placebo arm). At Day 14, significantly more patients had an absence of anterior chamber cells in the dexamethasone insert arm compared with placebo (52.3% versus 31.1%; P < .0001). At Day 8, significantly more patients had an absence of ocular pain in the dexamethasone insert arm compared with placebo (79.6% versus 61.3%; P < .0001). The dexamethasone insert arm showed no increase compared with placebo in incidence of all adverse events or ocular adverse events. Twice as many placebo patients required rescue therapy, compared with treated patients at Day 14., Conclusions: Both primary endpoints were successfully met. In addition, patients receiving the dexamethasone insert experienced a decrease in inflammation after surgery as early as Day 4 through Day 45, and a decrease in pain as early as one day after surgery (Day 2) through Day 45. The dexamethasone insert was well-tolerated, and the adverse events profile was similar to placebo., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the safety and efficacy of a 0.38% submicron formulation of loteprednol etabonate (LE) gel for the treatment of postoperative inflammation and pain after cataract surgery., Setting: Forty-five United States ophthalmology practices., Design: Double-masked vehicle-controlled randomized parallel group study., Methods: Patients 18 years of age or older with anterior chamber cells grade 2 or higher on day 1 after uncomplicated cataract surgery were randomized to 14 days of treatment with LE gel 2 times a day, LE gel 3 times a day, or vehicle. Hierarchical primary endpoints were the proportion of patients with resolution of anterior chamber cells and grade 0 (no) pain at postoperative day 8. Safety outcomes included adverse events, intraocular pressure (IOP), biomicroscopy, visual acuity, ophthalmoscopy, and tolerability (drop comfort and ocular symptoms)., Results: The intent-to-treat population included 514 patients. Significantly more patients in the LE gel 2 times a day and 3 times a day groups compared with the vehicle group had complete resolution of anterior chamber cells (26.9% and 28.7% versus 9.3%) and reported grade 0 pain (73.7% and 73.1% versus 47.7%) on day 8 (P < .001 vs vehicle for all). The safety findings were unremarkable, with 1 patient experiencing an IOP increase of 10 mm Hg or higher while on LE gel. More than 75% of patients in each group reported no drop discomfort., Conclusion: In this study, submicron loteprednol etabonate gel 0.38% appeared safe and effective in the treatment of postoperative inflammation and pain whether instilled 2 times or 3 times a day., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: To review current concepts regarding the mechanisms of postoperative pain after photorefractive keratectomy (PRK) and review available treatment options., Recent Findings: Many clinical studies have established the safety and efficacy of different topical and systematic therapeutic agents and techniques for the treatment of postoperative pain after PRK, especially topical nonsteroidal anti inflammatory agents and oral nonsteroidal and narcotic medications. New therapeutic agents and techniques are continuously studied, introducing new agents and comparing teh efficacy of different regimens. Postoperative pain severity varies widely between patients, and no single strategy has been proven best for acute pain management., Summary: To date, the literature supports the use of topical agents such as nonsteroidal anti-inflammatory medications (NSAIDs) and diluted topical anesthetics in combination with oral agents such as opiates and NSAIDs for acute pain management. The use of local agents and techniques is preferred due to their less significant side effect profile. The use of systemic opiate agents is reserved for breakthrough pain.

Study Objective: To determine if the number of emergency department (ED) rechecks, persistent fluorescein uptake, ophthalmology referrals, or complications would be affected by the prescription of topical tetracaine for pain relief from simple corneal abrasions (SCAs)., Methods: This retrospective cohort study was conducted in an ED where policy change allowed physicians to use topical tetracaine hydrochloride 1% eye drops for 24 hours for pain treatment for patients with corneal abrasions. Outcomes were compared between patients who did or did not received tetracaine (adjusting for the propensity for treatment)., Results: Of 1,576 initial ED presentations, 532 were SCAs, with 1,044 deemed nonsimple corneal abrasions (NSCAs). Tetracaine was dispensed at the initial visit for 303 SCA presentations (57%) and inappropriately for 141 NSCA presentations (14%). There were no serious complications or uncommon adverse events attributed to tetracaine for all SCAs and NSCAs combined (0/459; upper 95% confidence interval [CI] 0.80%). The relative risks (RRs) of ED recheck and fluorescein staining were increased overall among patients who received tetracaine (RR 1.67, 95% CI 1.25 to 2.23; and RR 1.65, 95% CI 1.07 to 2.53 for recheck and staining, respectively). However, the relative risks for only SCAs receiving tetracaine was 1.16 (95% CI 0.69 to 1.93) and 0.77 (95% CI 0.37 to 1.62), respectively. Referrals to ophthalmology were significantly decreased for all patients (SCAs and NSCAs) dispensed tetracaine (relative risk 0.33; 95% CI 0.19 to 0.59). The number of complications was too small to permit modeling., Conclusion: There was no evidence that up to 24-hour topical tetracaine for the treatment of pain caused by SCA was unsafe; however, CIs were wide and some increased risks were observed for NSCAs., (Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Venom ophthalmia is a condition that can be eyesight threatening. This article describes a case of venom ophthalmia due to the Naja pallida (red spitting cobra) and is aimed to educate readers regarding the management of an uncommon, yet important, pathology that deployed military personnel may encounter. Simple first steps can reduce the impact of the injury with copious irrigation of the eye being the key management step. Each step of the management, including what not to do, is discussed in order to educate and act as a guide to all deployed healthcare professionals., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To investigate the effect of nepafenac 0.3% in a once daily dosage regarding pain and healing after photorefractive keratectomy (PRK)., Methods: This was a prospective, comparative, contralateral randomized study of 35 patients undergoing PRK for the correction of low to moderate myopia and myopic astigmatism. After randomization, patients received nepafenac 0.3% ophthalmic suspension once daily in one eye (nepafenac 0.3% group) and nepafenac 0.1% ophthalmic suspension three times a day in the other eye (nepafenac 0.1% group) until the second postoperative day. Pain was evaluated every 2 hours on the day of the operation and then once daily using a scale ranging from 0 to 4. Patients were then examined at 2 weeks and 1, 3, 6, and 12 postoperative months. Visual acuity and subepithelial haze were also assessed., Results: No differences were detected between groups in pain scores, subepithelial haze scores, or visual acuity. Refractive predictability was also similar., Conclusions: Nepafenac 0.3% ophthalmic suspension in a daily regimen after PRK seems to be an effective treatment for pain and ocular discomfort with effects similar to the 0.1% suspension. [J Refract Surg. 2018;34(3):171-176.]., (Copyright 2018, SLACK Incorporated.)

Purpose: The purpose of this study was to compare the required supplemental anesthesia and postoperative patient pain score in individuals undergoing glaucoma surgery under topical anesthesia (TA) versus retrobulbar anesthesia (RB)., Materials and Methods: A retrospective, interventional, comparative cohort study of 261 eyes of 225 patients undergoing glaucoma and combined glaucoma with cataract surgery were included in the study. The main outcome measures were the amount of supplemental, systemic intraoperative anesthesia used and the postoperative pain scale between patients undergoing TA versus RB anesthesia. A secondary analysis was performed between combined glaucoma and cataract surgery versus glaucoma surgery alone., Results: About 6.2% patients complained of pain after glaucoma surgery (8.1% among TA group and 3.1% among RB group; P=0.049). Overall, pain tended to be mild with a mean score of 0.32 of 10 for TA and 0.08 of 10 for RB (P=0.027). The amount of IV anesthetics used intraoperatively was lower in the RB anesthesia compared with the TA group (midazolam, P=0.042; fentanyl, P<0.001; propofol, P<0.001). In addition, patients undergoing RB anesthesia were less likely to use postoperative pain medication (P<0.001). There was no difference in pain score (P=0.707) or in the amount of IV anesthetics (all P>0.350) between eyes undergoing combined versus glaucoma surgery alone., Conclusions: Although supplemental anesthesia and pain scores were statistically increased in the topical group, the prevalence and the severity of pain was low. Therefore, TA is feasible and a reasonable option for glaucoma surgery. Furthermore, this conclusion applies when glaucoma surgery is performed alone or in combination with the other eye surgery.