Effect of Oral Opioid Prescription on Rates of Postoperative Pain among Ophthalmology Subspecialties: A Large Database Analysis

Abstract

Purpose

To assess whether postoperative opioid prescriptions are associated with reduced pain diagnoses or emergency room (ER) visits after ophthalmic surgery.

Design

Retrospective cohort study using aggregated electronic health record data (June 2005–June 2025) from the TriNetX collaborative research network.

Subjects

Patients who underwent ophthalmic procedures across 11 subspecialty categories in the past 20 years, with or without a postoperative opioid prescription.

Methods

Data were analyzed using the TriNetX integrated analytics platform. Patients with chronic pain syndrome or opioid dependence were excluded. Ophthalmic procedures were identified using Current Procedural Terminology codes, and characterized as cataract; major or minor cornea, glaucoma, oculoplastics, trauma; retina; or strabismus. Associations were assessed by calculating absolute risk differences with 95% confidence intervals (CIs) and risk ratios.

Main Outcome Measures

Diagnosis of postprocedural pain or ER visits within 2 weeks after surgery.

Results

The study included 2 510 984 patients. Absolute rates of postoperative pain diagnoses were low across all subspecialties. Opioid prescriptions were associated with small absolute reductions in postprocedural pain diagnoses in glaucoma major (–1.3%, 95% CI: –1.4% to –1.2%, P < 0.001), oculoplastics major (–0.9%, 95% CI: –1.2% to 0.6%, P < 0.001), cornea major (–0.8%, 95% CI: –0.9% to –0.7%, P < 0.001), cornea minor (–0.8%, 95% CI: –0.8% to –0.7%, P < 0.001), trauma major (–0.8%, 95% CI: –0.9% to –0.6%, P < 0.001), trauma minor (–0.7%, 95% CI: –0.9% to –0.5%, P < 0.001), and oculoplastics minor (–0.1%, 95% CI: –0.2% to < –0.1%, P = 0.008) procedures. Emergency room visit reduction was observed only for glaucoma major procedures (–0.1%, 95% CI: –0.1% to < –0.1%, P < 0.001). In other subspecialties, opioid prescriptions were not associated with reduced ER utilization and were associated with higher ER visit rates in oculoplastics, retina, and trauma major procedures.

Conclusions

Postoperative opioid prescriptions were associated with small absolute reductions in pain diagnoses in selected subspecialties, including cornea, glaucoma, oculoplastics, and trauma, but not cataract, retina, or strabismus. Opioid prescriptions offered no consistent benefit in reducing ER visits and were linked to higher ER visit rates in some subspecialties. These findings highlight the limited clinical benefit of routine opioid prescribing after many ophthalmic procedures and underscore the need for subspecialty-specific, evidence-based postoperative pain management strategies in ophthalmology.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Since the 1990s, rising opioid use has contributed to a national public health crisis, marked by a dramatic increase in opioid-related deaths. According to the US Centers for Disease Control and Prevention, approximately 82 000 people died from opioid overdose in 2022—10 times the number reported in 1999.¹ Studies show that a large proportion of opioid dependence begins with prescription use and that perioperative exposure is linked to new persistent use among previously opioid-naïve patients.2, 3, 4 In response, many medical specialties have scrutinized perioperative opioid prescribing patterns. In ophthalmology, a large 2019 study found that opioid prescriptions filled after eye surgeries doubled between 2000 and 2014 despite procedures becoming less invasive.⁵ Moreover, patients who filled opioid prescriptions after ophthalmic surgery experienced higher rates of prolonged opioid use, overdose, hospitalization, and mortality compared to those who did not.^6,7

Efforts to address overprescribing—including new health care policies and greater awareness—have led to a gradual decline in prescription opioid rates in recent years.8, 9, 10, 11 Within ophthalmology, strategies such as retrobulbar anesthesia combined with perioperative IV or oral nonopioid analgesics have been shown to reduce postoperative opioid use.¹² Despite this, ophthalmologists still prescribe a substantial number of opioids,^7,13 even as questions remain about their postoperative effectiveness and necessity. Leveraging the advantages of a large aggregated electronic health record research network, this study examined whether postoperative opioid prescriptions reduce pain diagnoses and emergency room (ER) visits after ophthalmic surgery.

Methods

A retrospective cohort study was performed using TriNetX, a federated health research network comprising >130 million deidentified electronic medical records from 103 health care organizations. TriNetX aggregates patient data to protect patient confidentiality and is compliant with the Health Insurance Portability and Accountability Act. In instances where analysis yields <10 cases, TriNetX rounds the number of cases to 10 to ensure protection of data. This study did not involve human subjects as defined in 45 Code of Federal Regulations 46.102(e) or 21 Code of Federal Regulations 50.3(g). As such, this study was exempt from informed consent and approval from the Stanford University institutional review board because the study does not involve intervention or interaction with human subjects, and the data analyzed are deidentified per the deidentification standard defined in Section 164.514(a) of the Health Insurance Portability and Accountability Act Privacy Rule. This research adhered to the Declaration of Helsinki and all federal and state laws.

The data used in this study were collected from TriNetX on June 9, 2025. Retrospective review was conducted for subspecialty-specific ophthalmic surgeries occurring within the last 20 years. The analysis included patients with ophthalmic procedures identified by Current Procedural Terminology codes. The index event was defined as the surgical procedure that the patient underwent. The analyses were run separately on cohorts of patients classified into 11 subspecialty categories: cataract, cornea major, cornea minor, glaucoma major, glaucoma minor, oculoplastics major, oculoplastics minor, retina, strabismus, trauma major, and trauma minor (Table S1, available at www.ophthalmologyscience.org). Subspecialties were categorized as major or minor based on procedural invasiveness, expected recovery time, and complication risk. Only incisional-based procedures were included, and laser-only procedures were excluded.

Patients who were prescribed versus not prescribed oral opioid analgesics comprised the opioid and nonopioid groups, respectively. Groups were defined using RxNorm Anatomical Therapeutic Chemical codes: N02A (opioids; route oral product) and N02AX (other opioids; route oral product). The opioid group was defined as “must have” any of these medications, while the nonopioid group was defined as “cannot have” any of these medications. Oral opioids had to be prescribed within 1 week prior to and 1 day following the index event. This perioperative window was selected to capture prescriptions most likely intended for postoperative pain management; prescription fill data were not reliably available within TriNetX.

The primary outcome of interest was a diagnosis of acute postoperative pain using International Classification of Diseases, 10th Revision (ICD-10) code G89.18 (other acute postprocedural pain). This code was used to identify clinically significant pain promoting formal diagnosis rather than subjective pain severity. The secondary outcome of interest was ER visits identified using Current Procedural Terminology codes (99281, 1013711, 99283, 99284, 99282, and 99285). Outcomes were assessed from 1 to 14 days after the index surgery. Patients who had the outcome prior to the time window were excluded from analysis. Measures of association were calculated directly on the TriNetX platform. Risk differences with 95% confidence intervals (CIs) and risk ratios (RRs) were calculated. Patients with a diagnosis of chronic pain syndrome (ICD-10 G89.4) and opioid dependence (ICD-10 F11.2) were excluded from analysis. P values <0.05 were considered statistically significant. Baseline demographics such as age at index, sex assigned at birth, race, and ethnicity were summarized descriptively for each group without formal hypothesis testing.

Results

A total of 2 510 984 patients undergoing ophthalmic surgery over the period from June 2005 to June 2025 were identified in TriNetX. Baseline demographics by subspecialty and opioid exposure are displayed in Table S2, available at www.ophthalmologyscience.org. Cataract surgery comprised the largest proportion of procedures (25.9%), followed by cornea (major 13.5%, minor 15.0%), trauma (major 11.9%, minor 2.4%), glaucoma (major 8.9%, minor 2.5%), oculoplastics (major 1.1%, minor 9.6%), retina (5.8%), and strabismus (3.3%) procedures (Table S3, available at www.ophthalmologyscience.org). Opioid prescribing prevalence varied by subspecialty, occurring in 2.3% of cataract surgeries and approximately 6% to 16% of procedures across other subspecialties (Table S3).

Absolute rates of diagnosed acute postoperative pain were low across all subspecialties, ranging from 0.04% after cataract surgery to 2.2% after glaucoma major procedures (Table 1). Within the 2-week postoperative period, opioid prescriptions were associated with lower pain diagnosis rates in 7 subspecialty categories: glaucoma major (risk difference –1.3%; 95% CI: –1.4%, –1.2%; RR: 0.389; P < 0.001), oculoplastics major (–0.9%; 95% CI: –1.2%, –0.6%; RR: 0.369; P < 0.001), cornea major (risk difference –0.8%; 95% CI: –0.9%, –0.7%; RR: 0.477; P < 0.001), cornea minor (–0.8%; 95% CI: –0.8%, –0.7%; RR: 0.468; P < 0.001), trauma major (–0.8%; 95% CI: –0.9%, –0.6%; RR: 0.521; P < 0.001), trauma minor (–0.7%; 95% CI: –0.9%, –0.5%; RR: 0.408; P < 0.001), and oculoplastics minor (–0.1%; 95% CI: –0.2%, < –0.01%; RR: 0.741; P = 0.008) procedures (Table 1). No significant differences were observed for glaucoma minor (P = 0.815), retina (P = 0.458), or strabismus (P = 0.205). In the cataract surgery cohort, the opioid group demonstrated a very small but statistically significant increase in diagnosed postprocedural pain versus the nonopioid group (<0.1%; RR: 1.962; P = 0.02).

Table 1.

Number of Patients Developing Acute Postprocedural Pain

Surgery	Opioid Group			Nonopioid Group			Risk Difference % (95% CI)	Risk Ratio	Odds Ratio	P Value
	# In Cohort	# With Pain	Risk %	# In Cohort	# With Pain	Risk %
Cataract	15 036	12	0.08	614 716	250	0.04	<0.1 (<–0.1, 0.1)	1.962	1.963	0.02
Cornea major	45 690	336	0.74	280 371	4321	1.54	–0.8 (–0.9, –0.7)	0.477	0.473	0.000
Cornea minor	50 078	337	0.67	311 476	4478	1.44	–0.8 (–0.8, –0.7)	0.468	0.464	0.000
Glaucoma major	33 625	282	0.84	178 921	3861	2.16	–1.3 (–1.4, –1.2)	0.389	0.383	0.000
Glaucoma minor	3648	10∗	0.27	55 906	142	0.25	<0.1 (–0.2, 0.2)	1.079	1.079	0.815
Oculoplastics major	3295	18	0.55	21 344	316	1.48	–0.9 (–1.2, –0.6)	0.369	0.369	0.000
Oculoplastics minor	22 357	83	0.37	208 452	1044	0.50	–0.1 (–0.2, < –0.1)	0.741	0.740	0.008
Retina	11 946	34	0.28	128 099	319	0.25	<0.1 (–0.1, 0.1)	1.143	1.143	0.458
Strabismus	7453	13	0.17	73 521	184	0.25	–0.1 (–0.2, < 0.1)	0.697	0.696	0.205
Trauma major	36 415	298	0.82	249 395	3918	1.57	–0.8 (–0.9, –0.6)	0.521	0.517	0.000
Trauma minor	9319	46	0.49	46 749	566	1.21	–0.7 (–0.9, –0.5)	0.408	0.405	0.000

CI = confidence interval.

^∗To protect patient confidentiality, TriNetX does not report exact patient count values when they are ≤ 10.

We next compared the rates of ER visits in the 2-week postoperative period between the opioid group and the nonopioid group (Table 2). A significant risk reduction in the opioid group was seen in only 1 subspecialty category: glaucoma major (–0.1%; 95% CI: –0.1%, < –0.01%; RR: 0.323; P < 0.001). No significant difference was seen for cataract (P = 0.606), cornea major (P = 0.071), cornea minor (P = 0.050), glaucoma minor (P = 0.681), strabismus (P = 0.099), or trauma minor (P = 0.972). The opioid group had an increased risk of ER visit in the remaining subspecialty categories: oculoplastics major (risk difference: 1.1%; 95% CI: 0.6%, 1.5%; RR: 2.872; P < 0.001), oculoplastics minor (0.3%; 95% CI: 0.1%, 0.4%; RR: 1.889; P < 0.001), retina (0.3%; 95% CI: 0.1%, 0.4%; RR: 1.475; P = 0.001), and trauma major (< 0.1%; 95% CI: < 0.01%, 0.1%; RR: 1.973; P < 0.001).

Table 2.

Number of Patients with ER Visit

Surgery	Opioid Group			Nonopioid Group			Risk Difference % (95% CI)	Risk Ratio	Odds Ratio	P Value
	# In Cohort	# With ER Visit	Risk %	# In Cohort	# With ER Visit	Risk %
Cataract	12 763	49	0.38	459 150	1636	0.36	<0.1 (–0.1, 0.1)	1.077	1.078	0.606
Cornea major	46 705	11	0.02	288 261	119	0.04	<–0.1 (<–0.1, <–0.1)	0.571	0.570	0.071
Cornea minor	50 726	13	0.03	312 103	140	0.04	<–0.1 (<–0.1, <–0.1)	0.571	0.571	0.050
Glaucoma major	34 565	10∗	0.03	182 848	164	0.09	–0.1 (–0.1, <–0.1)	0.323	0.322	0.000
Glaucoma minor	3131	10∗	0.32	47 633	133	0.28	<0.1 (–0.2, 0.2)	1.144	1.144	0.681
Oculoplastics major	2755	45	1.63	19 870	113	0.57	1.1 (0.6, 1.5)	2.872	2.903	0.000
Oculoplastics minor	20 263	108	0.53	175 072	494	0.28	0.3 (0.1, 0.4)	1.889	1.894	0.000
Retina	9495	76	0.80	99 172	538	0.54	0.3 (0.1, 0.4)	1.475	1.479	0.001
Strabismus	6451	17	0.26	59 113	235	0.40	–0.1 (–0.3, < 0.1)	0.663	0.662	0.099
Trauma major	34 656	33	0.10	250 758	121	0.05	<0.1 (<0.1, 0.1)	1.973	1.974	0.000
Trauma minor	8160	34	0.42	40 585	168	0.41	<0.1 (–0.2, 0.2)	1.007	1.007	0.972

CI = confidence interval; ER = emergency room.

^∗To protect patient confidentiality, TriNetX does not report exact patient count values when they are ≤ 10.

Discussion

This large database study demonstrated that postoperative opioid prescriptions were associated with small absolute reductions in pain diagnoses in selected ophthalmic subspecialties, including glaucoma major, oculoplastics, cornea, and trauma. Across all ophthalmology subspecialties, the overall incidence of diagnosed acute postoperative pain was low, suggesting that adequate postoperative pain control is frequently achieved without opioid prescriptions. Even where statistically significant, absolute risk reductions were uniformly modest (≤1.3%), likely reflecting the large sample size rather than clinically meaningful benefit. Although relative RRs suggested sizable proportional reductions in some subspecialties, these occurred in the setting of low baseline event rates and therefore translate into minimal absolute benefit. Accordingly, absolute effects are emphasized to better convey clinical relevance.

Opioid prescriptions were not consistently associated with reduced ER utilization and were linked to an increased risk of ER visits in several subspecialties, including oculoplastics, retina, and trauma major. These findings should not be interpreted as causal. While the increased ER visits observed in this study cannot be directly attributed to opioid-related adverse events, this finding is consistent with prior literature demonstrating an association between opioid exposure and increased all-cause ER visits and hospitalizations.^6,14 However, increased ER utilization may also reflect residual confounding by surgical complexity or postoperative complications, heightened patient concern, or unrelated postoperative issues rather than opioid-related adverse events or inadequate pain control.

Although this study was not designed to directly compare opioid prescribing rates across ophthalmic subspecialties, observed opioid exposure rates varied substantially and were consistent with contemporary clinical practice, with the lowest rates following cataract surgery and higher rates following procedures typically associated with greater postoperative discomfort, including oculoplastics, trauma, and cornea. This pattern provides some reassurance that the exposure definition captures perioperative prescribing rather than unrelated opioid use. The subspecialties in which opioids were associated with significant pain reduction also correspond to those that are higher opioid prescribers. While opioid prescriptions overall comprise a low percentage of the total prescriptions written by ophthalmologists (4%), oculoplastics (which includes trauma) and cornea specialists are consistently found to be the highest opioid prescribers among ophthalmologists.^10,15, 16, 17 Surgical procedures within these subspecialties are generally considered to have higher expected postoperative pain levels, which are influenced by factors such as tissue type, extent of tissue trauma, invasiveness, and nerve involvement. Oculoplastic surgeons often perform invasive and complex procedures within the orbit, lacrimal system, eyelids, and other ocular adnexa, and these procedures can be associated with greater postoperative discomfort. Corneal surgical procedures may also lead to significant amounts of pain, as the cornea has more nerve endings than any other part of the body, and effective and safe pain control methods for the ocular surface remain limited.¹⁴ Appropriately managing pain is an important aspect of any surgeon’s care plan after painful procedures and is often linked to patient satisfaction. Although opioid prescriptions may be appropriate to control pain in certain cases, providers must weigh these benefits against their potential risks, including persistent use and misuse.

Efforts are actively underway in ophthalmology to continue to reduce the overprescribing of opioids through government intervention, professional society-endorsed guidelines, and institutional policy, while also meeting the pain control needs of patients.18, 19, 20 Recent studies have explored the advantages of opioid-free perioperative analgesia. A randomized controlled study by Zhang et al compared opioid-free analgesia using medial canthus peribulbar block combined with nonsteroidal anti-inflammatory drugs to opioid-sparing analgesia using low doses of fentanyl and nonsteroidal anti-inflammatory drugs in orbital fracture reconstruction surgery. They found opioid-free analgesia to not only be effective for postoperative pain relief but also to enhance the quality of early postoperative recovery.²¹ Similarly, studies have shown that IV ketorolac, pregabalin, and IV acetaminophen in the perioperative period reduce the need for opioids after oculoplastic procedures.^22,23 In strabismus surgery, subtenon block was found to significantly reduce the severity of early postoperative pain and decrease the number of children requiring postoperative opioid analgesia.²⁴ Another advantage was reduction in the incidence of postoperative vomiting and intraoperative oculocardiac events.²⁴ In cornea surgery, new emerging therapies such as autologous serum tears, human nerve growth factor, and endocannabinoid system modulators are being studied and may be effectively used in place of systemic oral opioids to control pain of the ocular surface.²⁵ These approaches may offer comparable pain control without the risks associated with systemic opioids. However, there is still a large unmet need for topical opioid-sparing therapy for patients with sequelae of surgery as well as chronic corneal pain, and further studies are needed to outline effective opioid-free perioperative pain management.

This study has several limitations inherent to its retrospective design and use of large, aggregated deidentified health records. First, it relied on diagnostic coding by providers; patients who experienced postprocedural pain but were not assigned the specific diagnosis code would be missed. Additionally, the analysis captured opioid prescriptions but could not capture opioid utilization because patient fill and refill data were not available within the database. Similarly, the analysis could not capture surgical complexity or intraoperative complications, which may influence opioid prescribing practices as well as postoperative pain. Second, we could not definitively attribute opioid prescriptions to the index surgical encounter within TriNetX. To partially mitigate this limitation, the timing of opioid prescription was limited from 1 week prior to 1 day after the index surgery, and patients with chronic pain syndrome and opioid dependence were excluded from the study, although comprehensive adjustment for all prior opioid exposure and all comorbid pain and psychiatric conditions was not feasible. Finally, we could not determine what the ER visits were for in the 2-week period following ophthalmic surgery. The visits could have been for acute postoperative pain, another postoperative complication, or for an unrelated condition.

Conclusions

Although postoperative pain diagnoses were uncommon across ophthalmic subspecialties, opioid prescriptions were associated with small absolute reductions in pain diagnoses in cornea, glaucoma, oculoplastics, and trauma procedures, but showed no benefit in cataract, retina, or strabismus surgeries. Notably, opioid prescriptions showed no consistent benefit in reducing ER visits—and sometimes increased them. Given the inconsistent and limited clinical benefits, combined with known risks of opioid exposure, these findings support continued development of data-driven, subspecialty-specific opioid prescribing guidelines in ophthalmology.

Manuscript no. XOPS-D-25-00674.