Treatment Response to Gabapentin in Neuropathic Ocular Pain Associated with Dry Eye

Abstract

Purpose: To investigate the response to gabapentin treatment in patients with dry eye (DE) accompanied by features of neuropathic ocular pain (NOP), and to analyze the differences between clinical manifestations of the groups according to treatment response. Methods: We retrospectively reviewed the records of 35 patients with DE accompanied by NOP features and obtained information on their medical history and previous ocular history. The patients underwent clinical examinations of the tear film, ocular surface, and meibomian gland and completed the Ocular Pain Assessment Survey (OPAS). One month after treatment with topical eye drops, add-on of gabapentin treatment was determined according to the Wong–Baker FACES Pain Rating Scale (WBFPS). A reduction of 2 points or more on the WBFPS was considered a positive treatment response. Enrolled patients were divided into three groups according to the treatment response: topical treatment response group (group 1, n = 11); gabapentin response group (group 2, n = 13); and gabapentin non-response group (group 3, n = 11). The medical history, clinical parameters, and OPAS scores were compared between groups. Results: The incidence of systemic comorbidities was higher in group 2 than in other groups. The corneal staining scores were lower in groups 2 and 3 than in group 1. Among the treatment response groups, group 2 showed improvements in OPAS scores of ocular pain severity, pain other than eyes, and quality of life, while group 1 showed improved OPAS scores of ocular pain severity and ocular associated factors. Group 2 exhibited lower scores of pains aggravated by mechanical and chemical stimuli than group 3. Conclusions: Gabapentin could be effective in patients who have systemic comorbidity and less pain evoked by mechanical and chemical stimuli for the treatment of DE patients with NOP, which is refractory to topical treatment.

Effects of Topical Gabapentin on Ocular Pain and Tear Secretion

“…However, the exact mechanism through which GBT, by involving multiple players, exerts its analgesic effect is complex and not definitively clarified ( Taylor and Harris, 2020 ). In ocular neuropathies, systemic administration of GBT or its analog pregabalin has been demonstrated to reduce pain ( Lichtinger et al, 2011 ; Pakravan et al, 2012 ; Wei et al, 2015 ; Ongun and Ongun, 2019 ; Yoon et al, 2020 ), although its efficacy in counteracting ocular pain in patients with DED has been questioned ( Ozmen, 2020 ).…”

“…Analgesic drugs include gabapentin (GBT), a structural analog of gamma-amino butyric acid that has been introduced as an adjunctive therapy in epilepsy and is presently widely used to treat several kinds of neuropathic pain. The possibility that GBT may counteract ocular pain has been suggested by several studies ( Lichtinger et al, 2011 ; Pakravan et al, 2012 ; Wei et al, 2015 ; Ongun and Ongun, 2019 ; Yoon et al, 2020 ), since the first demonstration of systemic GBT efficacy in providing significant pain relief in glaucomatous patients ( Kavalieratos and Dimou, 2008 ). At least some of the clinical effects of GBT are due to high affinity interactions with the α2δ1 auxiliary subunit of presynaptic voltage-gated calcium channels ( Taylor and Harris, 2020 ).…”

Topical TRPM8 Agonist for Relieving Neuropathic Ocular Pain in Patients with Dry Eye: A Pilot Study

“…However, these topical treatments appear to have limitations in producing an improvement in the corneal nerve morphologic status and central sensitization in patients with chronic NOP. Current systemic medication mainly includes oral antidepressants, anticonvulsants, or gabapentinoid; however, these systemic treatments have several limitations, such as delayed onset, variable efficacy, and unacceptable side effects [ 4 , 13 , 14 ]. In addition, limited data are available to support the use of systemic neuropathic pain medications for NOP associated with DE [ 14 , 15 , 16 ].…”

“…In addition, the wiping of C3 was more comfortable for patients than conventional instillation of eye drops, and produced a painless cooling sensation lasting approximately 40 min [ 9 ]. The OPAS scores also decreased at 1 week after treatment, indicating that the topical drug produces effect faster than systemic drugs do [ 14 ]. Moreover, although the effect was temporary, C3 was particularly effective when the patients experienced severe pain due to DE, such as when driving or sleeping, thereby resulting in an improved QoL.…”

Corneal Nerve Abnormalities in Painful Dry Eye Disease Patients

“…The concept of "neuropathic corneal pain" (NCP), increasingly investigated in the past 20 years in clinical research [4,14], has been suggested to play a central role in those cases. NCP represents a current clinical challenge, as those patients are commonly not responding to classic dry eye treatments [15], and the ocular pathology is often associated with depressive disorders [16].…”