Ocular Pain After Refractive Surgery: Interim Analysis of Frequency and Risk Factors

Betz J, Behrens H, Harkness B et al. Ophthalmology 2023; 130:692-701

Question

At what frequency does prolonged postoperative pain develop in refractive surgery patients and what predictors of prolonged postoperative pain are available?

Background/Summary of Findings

Both LASIK and photorefractive keratectomy are associated with potential for prolonged postoperative pain. Historically, this pain has been widely attributed to dryness of the eye. Over time, the root cause of dryness has been questioned because much of the pain is described as subjectively different from how patients with dry eye typically report pain, and signs of dryness are also often lacking. This multicenter prospective study used subjective pain ratings, validated dry-eye questionnaires (both 5-Item Dry Eye Questionnaire and Ocular Surface Disease Index), and a detailed clinical assessment of the ocular surface at various times throughout the perioperative period (preoperatively through the 6-month postoperative appointment).

Twenty-eight percent of patients reported pain the day after surgery (self-reported as 3 or higher on a 0-10 pain scale). Interestingly, this number was not different for patients receiving LASIK or photoreactive keratectomy. Over time, 25% of patients still had pain at either the 3- or 6-month postoperative visit, and 11% reported pain at both of those visits (this 11% group was defined as having prolonged postoperative pain). These symptoms did not correlate to dissatisfaction with vision or subjective clinician assessment of the ocular surface. Topical anesthesia usually eliminated pain, which, when paired with uninvolved ocular surfaces, points to peripheral neuropathic origins of post–refractive surgery pain. Risk factors for prolonged postoperative pain were 1) ocular pain immediately prior to surgery; 2) symptoms of depression prior to surgery; 3) oral antihistamine use prior to surgery; and 4) ocular pain the day after surgery.

Clinical Value/Implications

This review is interesting as it confirms that prolonged postoperative pain after refractive surgery, which has historically been attributed to worsening dryness of the ocular surface, cannot be objectively linked to dryness and is more likely to be neuropathic in origin. Furthermore, key preoperative risk factors of prolonged postoperative pain were identified and can be used for counseling patients more specifically regarding their individual risk of developing prolonged postoperative pain.

Madjedi KM, Stuart KV, Chua SY, et al. Ophthalmology 2023;130(10):1024-1036.

Questions

  1. What is the association between physical activity, glaucoma, and glaucoma-related traits?

  2. Does genetic predisposition to glaucoma modify these traits and is there a causal relationship that can be detected using Mendelian randomization?

Background/Summary of Findings

This was a cross-sectional observational and gene-environment interaction analysis in the UK Biobank employing two-sample Mendelian randomization experiments using summary statistics from large genetic consortia. Included were data from UK Biobank participants on self-reported or accelerometer-derived physical activity, intraocular pressure, macular inner retinal optical coherence tomography measures, and glaucoma status. The authors evaluated multivariable adjusted associations of physical activity with intraocular pressure and inner retinal optical coherence tomography parameters using linear regression and evaluated glaucoma status using logistic regression. They also examined gene–physical activity interactions using a polygenic risk score that combined the effects of 2673 known genetic variants associated with glaucoma.

In multivariable-adjusted regression models, the authors found no association between the amount or level of physical activity and glaucoma status or mean macular retinal nerve fiber layer thickness. Furthermore, glaucoma polygenic risk score did not modify any of the associations, and Mendelian randomization analyses did not support any causal relationship between physical activity and any glaucoma-related outcome. Additionally, there were only modest and inconsistent intraocular pressure associations with physical activity. However, greater and more vigorous overall physical activity levels and time spent engaged in physical activity was positively associated with thicker mean ganglion cell-inner plexiform layer when compared with participants with the lowest amount and intensity of physical activity.

Clinical Value/Implications

There is a desire to find modifiable risk factors in the management of glaucoma beyond standard use of ocular hypotensive medications. Additionally, as more genetic information is unlocked and we aspire to more and more personalized medicine, the interaction between genetics, various disease states, and disease modification warrants exploration. Previous studies have shown that lifestyle modifications, specifically, increased physical activity duration and intensity, result in an acute and transient decrease in intraocular pressure. This cross-sectional analysis did not support any significant relationship between habitual physical activity, glaucoma status, and intraocular pressure. Accordingly, any short-term decrease in intraocular pressure from physical activity may not translate into a sustained effect. Interestingly, the strong relationship between physical activity and thicker mean ganglion cell-inner plexiform layer may strengthen the argument for physical activity’s potential role in neuroprotection. Therefore, in this study, physical activity as a glaucoma modifier may have value in direct preservation of neural tissue, rather than in reducing intraocular pressure to modify neural tissue loss.

Fourteen-Year Outcome of Angle-Closure Prevention With Laser Iridotomy in Zhongshan Angle Closure Prevention Study: Extended Follow-up of a Randomized Controlled Trial

Yuan Y, Wang W, Xiong R, et al. Ophthalmology 2023 Aug;130(8):786-794.

Question

Does initial prophylaxis for primary angle-closure suspects result in a decreased incidence of conversion to primary angle closure over a 14-year study period?

Background/Summary of Findings

Four hundred ninety-nine of an original 889 post–laser peripheral iridotomy eyes from the original 6-year Zhongshan Angle Closure Prevention Study were monitored from years 7 to 14. Fourteen of them reached the primary outcome of primary angle closure, which was 1) repeatable intraocular pressure > 24; 2) peripheral anterior synechiae ≥ 1 clock hour in either quadrant; or 3) acute angle closure crisis. Of 501 of an original 889 control eyes, 69 eyes reached the primary angle closure endpoint. Notably, between years 7 and 14 of the study, two eyes achieved primary angle closure based on reaching >24 mm Hg and 81 eyes achieved primary angle closure based on developing peripheral anterior synechiae. Zero eyes developed acute angle closure crisis between 7 and 14 years.

Overall, the 14-year rate of reaching primary angle closure was low; however, eyes treated with laser peripheral iridotomy did have a 69% reduced risk of developing primary angle closure when compared with the control group. This was driven primarily by the development of peripheral anterior synechiae in the control eyes at a 3× greater incidence than in the laser peripheral iridotomy–treated eyes. The number needed to treat was 12.35 to prevent one primary angle closure occurrence over 14 years, whereas it was 44 after the original 6-year phase.

Clinical Value/Implications

After 14 years the Zhongshan Angle Prevention Study trial concluded that although prophylactic laser peripheral iridotomy reduced the risk of primary angle closure by two-thirds over 14 years, the incidence of primary angle closure itself was low. With a number needed to treat of 12.35, any decision to treat indiscriminately seems to be unreasonable. Those with higher risk profiles are more likely to benefit from early intervention. From a practitioner standpoint these study results recognize that both observation and intervention can be reasonable approaches to patients with primary angle-closure suspects. A shared decision-making approach and best attempt at individualized care should be the approach. The angle should be monitored for the development of peripheral anterior synechiae in untreated cases, and both the extent of angle widening post-treatment and subsequent contracture overtime should be monitored in those undergoing laser peripheral iridotomy.

Reticular Pseudodrusen Status, ARMS2/HTRA1 Genotype, and Geographic Atrophy Enlargement

Agron E, Domalpally A, Cukras CA, et al. Ophthalmology 2023;130:488-500

Questions

  1. Is there an association between reticular pseudo-drusen status, ARMS2/HTRA1 genotype, or both with altered geographic atrophy enlargement rate?

  2. Does reticular pseudo-drusen status mediate genetic effects?

Background/Summary of Findings

This was a post hoc analysis of an age-related eye disease 2 cohort, specifically analyzing 771 eyes of 563 participants with geographic atrophy. Geographic atrophy and its enlargement were evaluated by color fundus photography, reticular pseudodrusen was evaluated by fundus autofluorescence, and genetic data were analyzed using a custom Illumina HumanCoreExome array. The main outcome was the change in square root of geographic atrophy area.

The authors found that geographic atrophy enlargement was significantly faster in eyes with reticular pseudodrusen and in individuals carrying ARMS2/HTRA1 risk alleles. Specifically, the enlargement rate was 35% faster in eyes with reticular pseudodrusen versus those without and was consistent in both recently developed and chronic geographic atrophy cases. The same rate difference was noted in patients with two risk alleles versus those with none. The presence of reticular pseudodrusen was not shown to mediate the relationship between ARMS/HTRA1 and faster enlargement, and thus, these two factors appear to be independent of each other despite their common association with faster enlargement. The post hoc analysis also revealed that the presence of reticular pseudodrusen is most associated with faster progression of atrophy directed toward the central macula and does not predict the focality or central involvement of the geographic atrophy lesions. Last, the authors note that, given reticular pseudodrusen’s prognostic value, genetic testing may not be necessary.

Clinical Value/Implications

The presence of reticular pseudodrusen, anatomically more appropriately known as subretinal drusenoid deposits, has recently risen to prominence as a negative prognostic indicator in age-related macular degeneration. This analysis reinforces the necessity of first detecting and then considering the presence of reticular pseudodrusen in patients with geographic atrophy. The presence of reticular pseudodrusen should be an important part of determining care intervals as well as how we educate our patients on their atrophic age-related macular degeneration.

The Impact of Social Determinants of Health on Eye Care Utilization in a National Sample of People With Diabetes

Taccheri C, Jordan J, Tran D, et al. Ophthalmology 2023 Jun 15; S0161-6420(23)00425-6

Question

What is the association of a comprehensive set of social determinants of health with eye care use among a nationally representative set of people with self-reported diabetes?

Background/Summary of Findings

Social determinants of health are the conditions in which people live, work, and play within the broader umbrella of economic systems and social structures, all of which influence daily living conditions. Research shows that social determinants of health play a significant role in health care outcomes and warrant consideration when evaluating a patient’s overall health status. Specifically, diabetic retinopathy prevalence has been shown to be associated with social determinants of health, with those same social determinants of health associated with underuse of eye care services.

This study employed a retrospective cross-sectional design and included participants >18 years of age with self-reported diabetes according to their responses to the 2013-2017 National Health Interview Survey questionnaires. Social-determinants-of-health burden was determined using an aggregate social-determinants-of-health score that comprised the following domains: 1) economic stability; 2) neighborhood, physical environment, and social cohesion; 3) community and social context; 4) food environment; 5) education; and 6) health care system. Social-determinants-of-health scores were divided into quartiles, and multivariable logistic regression models evaluated the association between those individual quartiles and respondent eye care use within the preceding 12 months.

The study found that 43% of 20 807 adults with self-reported diabetes who had participated in the National Health Interview Survey had not used eye care in the previous 12 months. Additionally, patients within the highest social-determinants-of-health burden quartile had 59% lower odds of using eye care when compared with the lowest burden quartile.

Clinical Value/Implications

This study’s results further bolster the conclusion that social determinants of health have a negative effect on our patients’ health care status and provide potential target metrics, which may assist efforts to identify those at greatest risk of not using eye care. Focusing on increasing eye care use in patients with diabetes with higher social-determinants-of-health burden has the potential to reduce the threat of vision loss from diabetic retinopathy, which often remains undetected in these groups due to lack of examination.