Efficacy of topical 0.05% cyclosporine A and 0.1% sodium hyaluronate in post-refractive surgery chronic dry eye patients with ocular pain.

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-1ß, 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.

FL-41 Tint Reduces Activation of Neural Pathways of Photophobia in Patients with Chronic Ocular Pain.

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.

Effects of Mirogabalin on Hyperalgesia and Chronic Ocular Pain in Tear-Deficient Dry-Eye Rats.

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.

Novel Treatments for Chronic Ocular Surface Pain.

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.

Details and outcomes of a large cohort of MOG-IgG associated optic neuritis.

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.

Pathogenic Mechanism of Dry Eye-Induced Chronic Ocular Pain and a Mechanism-Based Therapeutic Approach.

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.

Is there a rational basis for cannabinoids research and development in ocular pain therapy? A systematic review of preclinical evidence.

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.

Opioid Prescribing Patterns for Ulcerative Keratitis.

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.

Opioids and ophthalmology: review of the current literature.

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.

Cannabis and the Cornea.

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.

Is gabapentin effective in dry eye disease and neuropathic ocular pain?

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.

Dupilumab-Associated Ocular Surface Disease: Clinical Characteristics, Treatment, and Follow-Up.

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.

Short-Term Topical Tetracaine Is Highly Efficacious for the Treatment of Pain Caused by Corneal Abrasions: A Double-Blind, Randomized Clinical Trial.

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.

Use of gabapentin in management of postoperative pain after crosslinking / Uso da gabapentina no manejo da dor pós-operatória do crosslinking

ABSTRACT Objective: The objective was to evaluate the efficacy of gabapentin in the management of neuropathic pain in patients with keratoconus, who were treated with fast (10 minutes) epi-off corneal crosslinking (CXL). Methods: This was a prospective, double-blind, randomized study. The sample comprised patients with bilateral progressive keratoconus, aged 12 years or older, who underwent a bilateral epi-off corneal CXL (fast - 10 minutes) procedure. One group was given placebo orally, and the other group received gabapentin 600 mg orally, both preoperatively. The visual analogue scale (VAS) was applied to record postoperative pain up to 48 hours after procedure. The study was conducted at the Belotto Stock Centro Oftalmológico, in the city of Joaçaba, Santa Catarina, Brazil, from June 2018 to September 2019. Results: At no point in the study significant differences were observed between groups, in terms of pain intensity measured by means of the VAS questionnaire, or of opioid use (Paco®), though opioid consumption was 21% lower in the group receiving gabapentin. Conclusion: We concluded gabapentin has no efficacy in postoperative pain control after epi-off corneal CXL (fast - 10 minutes). Although there was no statistically significant difference, the group that received gabapentin suffered less pain, resulting in lower opioid consumption. UTN number: U1111-1256-0330.

RESUMO Objetivo: Avaliar a eficácia do uso da gabapentina no manejo da dor neuropática em pacientes portadores de ceratocone submetidos ao tratamento de crosslinking corneano epi-off fast de 10 minutos. Métodos: Tratou-se de pesquisa prospectiva, duplo-cega, randomizada. A amostra foi composta de pacientes com ceratocone progressivo bilateral, a partir dos 12 anos de idade, submetidos ao procedimento de crosslinking corneano acelerado epi-off fast de 10 minutos bilateral. Um grupo recebeu placebo via oral e o outro, gabapentina 600mg, via oral, ambos no pré-operatório. A Escala Visual Analógica foi aplicada para registrar a dor pós-operatória até 48 horas após o procedimento. A pesquisa foi realizada no período de junho de 2018 a setembro de 2019 em um centro oftalmológico. Resultados: Não foram observadas diferenças estatísticas significativas para ambos os grupos, tanto na intensidade da dor medida pela Escala Visual Analógica, como na redução do uso do opioide (Paco®), em qualquer horário analisado durante um período de 48 horas. No entanto, houve redução de 21% no consumo de opioides pelo grupo que fez uso da gabapentina. Conclusão: A gabapentina não demonstrou eficácia no controle da dor no pós-operatório do crosslinking corneano epi-off fast de 10 minutos. No entanto, observou-se que, mesmo não havendo diferença estatisticamente significativa, houve diminuição da dor no grupo em que foi usada a gabapentina, resultando na redução do consumo de opioides. Número UTN: U1111-1256-0330.

Topical treatment with a mu opioid receptor agonist alleviates corneal allodynia and corneal nerve sensitization in mice.

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-Ala2,N-Me-Phe4,Gly5-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.

Efficacy and tolerability of nortriptyline in the management of neuropathic corneal pain.

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.