Should Patients With Optic Disc Drusen Be Treated With Intraocular Pressure-Lowering Medications?

Optic disc drusen are a relative common finding in patients presenting to a neuro-ophthalmology clinic. Although symptomatic visual loss is uncommon, some patients with disc drusen develop progressive visual field loss

Point Counter-Point Section Editors: Andrew G. Lee, MD Gregory P. Van Stavern, MD Should Patients With Optic Disc Drusen Be Treated With Intraocular Pressure–Lowering Medications? Julie M. Falardeau, MD, Stacy L. Pineles, MD, Gregory P. Van Stavern, MD, Andrew G. Lee, MD Optic disc drusen are a relative common finding in patients presenting to a neuro-ophthalmology clinic. Although symptomatic visual loss is uncommon, some patients with disc drusen develop progressive visual field loss. There is debate about whether medications to lower intraocular pressure should used to stabilize visual function and prevent visual field loss in patients with disc drusen. Two experts discuss this topic. Pro: Stacy L. Pineles, MD Optic disc drusen (ODD) are present in 0.5%–3.7% of the population (1,2). Although the definitive etiology of ODD is not known, proposed risk factors include a small scleral canal, dysplasia of the optic nerve and its vasculature, and small optic disc size. Impairment of axonal transport in an optic nerve which may be congenitally abnormal, in conjunction with mechanical compression of the retinal nerve fibers from the drusen, and decreased perfusion of the optic nerve head place patients with ODD at risk of optic neuropathy and resultant retinal nerve fiber layer (rNFL) thinning and subsequent visual field defects (1). Visual field defects are common in patients with ODD, with a prevalence ranging from 24% to 87%, depending on the population studied (1). However, similar to glaucomatous visual field loss, patients are typically not aware of the defects or of subsequent deterioration. Despite the high frequency of visual field loss and the potential for deterioration (16%–22%), there are no definitive treatments or prophylactic measures currently in widespread use (3,4). Intraocular pressure (IOP)-lowering therapy has been used successfully in the treatment of other optic neuropathies without ocular hypertension (OHT), most notably in normal tension glaucoma (NTG). Although a review of the pathogenesis and treatment of NTG is outside the scope of this article, current conceptualization includes multiple theories encompassing a possible higher sensitivity to “norDepartment of Ophthalmology (JMF), Portland, Oregon; Department of Ophthalmology (SLP), UCLA, Los Angeles, California; and Department of Ophthalmology and Visual Sciences (GPVS), Washington University in St. Louis, St. Louis, Missouri. S. L. Pineles: Support provided by Unrestricted Funds from Research to Prevent Blindness. The authors report no conflicts of interest. Address correspondence to Gregory Van Stavern, MD, Department of Ophthalmology and Visual Sciences, Washington University in St. Louis, 660 S. Euclid Avenue, St. Louis, MO 63130; E-mail: [e-mail]. 538 mal” IOP, vascular dysregulation, an abnormally high translaminar pressure gradient or a neurodegenerative process due to impaired cerebrospinal fluid dynamics (5). Since several of these concepts result in decreased perfusion pressure of the optic nerve, there are some similarities to optic neuropathy associated with ODD. The Collaborative Normal-Tension Glaucoma Study revealed that lowering the IOP by 30% from baseline in patients with normal IOP improved risk of visual field progression with 40% visual field progression in the treatment group vs 80% in control subjects over 5 years (6). Although NTG and ODD are distinct entities and entirely different diseases, this study set a precedent for lowering IOP beyond “normal” levels in certain cases. Patients with ODD are at risk of rNFL loss due to altered retinal circulation from congenital retinal vascular anomalies as well as decreased blood flow velocity through perioptic nerve arterioles (7). Theoretically, lowering IOP beyond normal levels could improve optic nerve perfusion pressure, which may in turn improve rNFL resilience when taxed by mechanical factors from the ODD. Grippo et al evaluated the impact of IOP on visual field loss in patients with ODD (8). Twenty-two eyes of 13 patients with coexistent ODD and OHT (IOP . 21 mm Hg based on maximum recorded tonometry) were compared with 81 eyes of 47 patients with normal IOP. The results revealed that visual field loss was significantly associated with OHT (90% of eyes with elevated IOP vs 67% of eyes with normal IOP exhibited visual field loss, P = 0.03). Given that this study demonstrated a significant role for IOP in visual field loss in patients with ODD, it follows that some clinicians may wish to consider IOP lowering in all patients with ODD, since thresholds for elevated IOP may be somewhat arbitrary and likely vary based on patientspecific individual parameters. Although rare, ODD may coexist with glaucoma, and this may present a challenge for ophthalmologists who wish to serially assess the optic Falardeau et al: J Neuro-Ophthalmol 2020; 40: 538-543 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Point Counter-Point nerve and visual field. The ODD and configuration of optic nerve can mask progressive cupping, and pre-existing ODD-related visual field (VF) defects may confound the progression of glaucomatous defects. This conundrum argues for a very low threshold for treatment with IOPlowering medications in patients with ODD suspected of having coexistent glaucoma. In 2017, Pojda-Wilczek and Wycislo-Gawron published the results of a study in which 34 patients with bilateral ODD who did not have OHT or glaucoma underwent treatment with brinzolamide in the eye with more advanced optic neuropathy (more advanced visual field defect) from ODD (9). The fellow eye, which also harbored ODD, was used as a paired control. After 1 year of treatment and observation, a comparison of rNFL thickness, pattern electroretinogram (pERG), and static perimetry between the treated and fellow eyes was performed. At baseline, there was no significant difference between the IOP of the study and fellow eyes. However, after 1 year of treatment, the treated eyes had a mean decrease in IOP of 5.94 vs 1 mm Hg in the control eyes (P , 0.001). Regarding visual field parameters, the mean deviation (MD) was not significantly different between the 2 groups at baseline; however, after 1 year of treatment, the MD improved significantly in the study eyes (P = 0.0378) but not in the control eyes (P = 0.2058). Interestingly, the mean rNFL thickness remained stable in the study eyes but decreased significantly (from 83.21 ± 20.37 to 79.85 ± 21.41 mm, P = 0.0017) in the untreated fellow eyes. In addition, the median N95 wave amplitude on pERG improved significantly in the study eyes but not in the fellow eyes. The authors posited that the N95 wave amplitude improvement that occurred only in the treated eyes was indicative of an improvement in retinal ganglion cell function. In a similar study, Schargus and Gramer (10) compared 16 patients with ODD who had undergone IOP-lowering therapy to 16 patients who had not been treated and found that there was a significantly slower progression of visual field loss in eyes treated with IOP-lowering therapy. Most recently, Nolan et al studied the relationship between IOP and optic nerve structure by retrospectively reviewing the records of 146 patients (236 eyes) with ODD (11). This study used a logistic regression model to evaluate the association of elevated IOP with rNFL and visual field parameters. Although the study failed to find an association between IOP and rNFL or visual field loss, the authors concede that there are many flaws in the study leading to doubt with regards to its conclusions. Importantly, this study was a cross-sectional study, and the impact of IOP on the optic nerve with ODD may be more of a longitudinal effect, with visual field loss or rNFL thinning occurring over a period. Previous studies have shown that the average time interval for significant visual field change in patients with ODD is close to 9 years (12). In addition to the IOP-lowering aspect of therapy, brimonidine may also have a secondary treatment effect for patients with ODD. Animal studies have demonstrated that administration of alpha-2-receptor agonists specifically activate pathways that exert measurable neuroprotective effects in the retina. In various models of optic nerve injury including crush, compression, and OHT, these agonists appear to have a role in neuroprotection (13). However, despite this promising work, there has not been convincing data proving similar efficacy in humans. Therefore, the neuroprotective aspect of treatment is still hypothetical. Given the potential benefits and low likelihood of risk, I believe that it is reasonable to treat patients with ODD who already show signs of optic nerve compromise such as rNFL thinning or visual field loss with IOPlowering therapy. There is a lack of high-quality data to support either side of this debate, and so, we must ask ourselves: if patients are at risk of severe vision loss and are also at risk of rNFL loss simply from harboring drusen (14,15), what is the downside of prophylactically lowering their IOP to improve optic nerve perfusion and also in some cases to provide possible neuroprotection? In studies of NTG and OHT, lowering of the IOP led to better outcomes despite the lack of compelling factors for treatment (lack of visual loss in OHT and lack of OHT in NTG). Therefore, I would suggest that IOPlowering therapy also be considered in patients at risk of optic neuropathy from ODD. Con: Julie M. Falardeau, MD ODD are acellular deposits of calcium, amino and nucleic acids, and mucopolysaccharides located in the prelaminar portion of the optic nerve head (16). Visual field defects have been reported in up to 87% of adults and up to 51% of children with ODD and are more likely to be observed in eyes with visible drusen (2,8,17–20). In a study of 92 eyes with ODD, Wilkins and Pomeranz (2) reported 73% of optic discs with visible drusen had abnormal visual fields compared with only 36% of optic discs with buried drusen. Falardeau et al: J Neuro-Ophthalmol 2020; 40: 538-543 The most common visual field defects reported in their study were nerve fiber bundle in type, the majority in inferonasal sectoral and inferior arcuate distributions. Other commonly observed visual field defects include enlarged blind spot and generalized constriction (2). Children with ODD have similar patterns of visual field defects, and as seen with the adult form, visual field constriction is more likely to occur with superficial drusen (21). Longitudinal studies of visual field defects in optic disc drusen suggest 539 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Point Counter-Point that progression is generally slow and visual acuity is rarely impaired (22,23). Needless to say, there are several commonalities between ODD and glaucomatous optic neuropathy. Given these similarities, it has been proposed that IOP-lowering agents may be beneficial for visual field defects related to ODD, similar to reducing the risk of progression in glaucomatous optic neuropathy. Furthermore, some clinicians routinely prescribe brimonidine in patients with ODD (regardless of the IOP reading), not only for its IOP-lowering effect but also for its presumed neuroprotective benefit. Here are some major issues related to treatment of ODD with IOP-lowering agents in normotensive eyes: 1. Although there are many similarities between ODD and glaucomatous optic neuropathy, we cannot extrapolate the results of glaucoma clinical trials to justify the use of IOP-lowering agents in normotensive ODD eyes. There is currently a lack of good evidence to support such therapy in patients with ODD. 2. There is significant cost associated with long-term use of IOP-lowering agents, not to mention the potential side effects of such treatment. 3. There is little proof of a neuroprotective effect from brimonidine in human studies. 4. The finding of retinal nerve fiber layer (RNFL) thinning using optical coherence tomography (OCT) has been used by some clinicians as an indication of glaucoma, consequently justifying treatment with IOP-lowering agent despite the fact that several studies have demonstrated that drusen alone can cause loss of RNFL (11,24). Chang and Pineles (20) have proposed ocular hypotensive therapy in patients with progressive visual field defects secondary to optic disc drusen. However, they acknowledge that there have been no studies to evaluate the effectiveness of this therapy in children or adults. Although there may be similarities between glaucoma and ODD, there are also major differences in pathophysiology, as indicated by some studies. Abegao Pinto et al (7) looked at retrobulbar hemodynamics in patients with primary open angle glaucoma and in patients with ODD and found that in subjects with ODD, the central retinal artery (CRA) blood flow velocity patterns correlated with the extent of the visual field defects. This finding was not seen in their glaucoma subjects. Patients with ODD had lower systolic and diastolic flow velocities in the CRA when compared with healthy individuals, but no difference was found with the glaucoma group. With a median follow‐up period of 56 years, a study by Malmqvist et al (25) suggests that the evolution of ODD involves a transition phase in adolescence, during which visual field defects may rapidly progress with minimal worsening thereafter. This is clearly different from studies looking at progression of glaucomatous optic neuropathy, 540 consistently showing that older age is a risk factor associated with the development of primary open angle glaucoma (26). Relation between intraocular pressure and optic nerve function in ODD In a cross-sectional study of 103 eyes with ODD, Grippo et al (8) found that visual field loss was present in 90.9% of hypertensive eyes (IOP $22 mm Hg) and 66.7% of normotensive eyes. Logistic regression analysis indicated that OHT and Grade III ($7 visible drusen) were independently and significantly associated with visual field loss. They recommended that individuals with ODD and OHT receive IOP-lowering therapy to prevent progression of visual field loss. However, such recommendation was not made for normotensive eyes with ODD. Furthermore, this study did not look at the reduced risk of progression over time when patients were in fact treated with topical glaucoma agents. A recent study by Nolan et al (11) looked for a potential correlation between IOP and perimetric MD (PMD) and between IOP and mean RNFL thickness on OCT in patients with ODD. The average PMD of 236 eyes was 25.22 dB, and the mean IOP was 15.7 mm Hg (range: 6–24 mm Hg). The mean RNFL thickness was 79.9 mm. There was no statistically significant association between IOP and PMD or RNFL thickness. Interestingly, their study found a significant correlation between the presence of OHT and less depressed PMD among all eyes and the visible ODD subgroup (P = 0.038 and 0.035, respectively). They concluded that lowering IOP in normotensive eyes might not be beneficial in preventing vision loss in patients with ODD. Brimonidine-related neuroprotection: a myth? Some clinicians advocate the routine use of brimonidine, an alpha-2 adrenergic agonist, in patients with ODD for its IOP-lowering and neuroprotective effects. Experimental models suggest that brimonidine confers neuroprotection in several types of ocular injury, including ischemia-induced injury, optic nerve compression or optic nerve crush injury, photoreceptor degeneration, and OHT and glaucoma. However, there is little proof of neuroprotection in comparable human studies (13). Clinical trials looking at the potential of brimonidine as neuroprotective agent in nonarteritic anterior ischemic optic neuropathy and Leber hereditary optic neuropathy reported unsuccessful results. A recent Cochrane review did not find any strong evidence to support a neuroprotective effect from brimonidine in adults with open angle glaucoma (27). Cost-effectiveness of treating ODD with intraocular pressure–lowering agents A study looking at the cost-effectiveness of treating OHT showed that based on the results and practice patterns of the Falardeau et al: J Neuro-Ophthalmol 2020; 40: 538-543 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Point Counter-Point Ocular Hypertension Treatment Study, treating all OHT patients was not cost-effective (28). How can we justify the cost-effectiveness of treating ODD when there is actually no study proving its efficacy in reducing the risk of progressive visual field loss? A recent study showed that glaucoma medications generated the highest total costs of any single category of ophthalmic medications (29). The median cost per 1month supply of glaucoma medication was $75 (IQR, $19–$121; range, $2–$1,387). Brand medications accounted for 75% of the total glaucoma medication cost. The average cost for brand brimonidine tartrate for a 30day supply is $118, $126 for latanoprost, and $143 for timolol maleate, to name a few (19). The cost associated with daily use of a topical glaucoma agent over the course of years is clearly significant, and yet, studies looking at rate of visual field progression in eyes with ODD showed minimal changes during adult life (25). Shelton et al (22) examined 23 untreated eyes with ODD over a mean of 9.7 years and found the average change in PMD on Humphrey visual field to be 20.78 dB, with most eyes showing no clinically significant decrease in MD (only 3 eyes demonstrated more than a 3 dB decrease). In summary, no effective treatment of ODD has yet been established (16). Although IOP-lowering agents are a reasonable therapy for hypertensive eyes with ODD, the routine use of IOP-lowering drugs should not be adopted by clinicians until we have compelling data demonstrating the benefit of such treatment in reducing the risk of progressive visual field loss. Rebuttal: Stacy L. Pineles, MD Dr. Falardeau has done a magnificent job of outlining the major reasons not to routinely treat patients with ODD with IOP-lowering agents. I agree with many of her points and would concede that in patients with normal to low IOP and no VF defect, it is very reasonable to observe. Furthermore, we both agree that glaucoma and ODD are different diseases and despite some similarities, should not be classified together. However, I would disagree that the lack of evidence to support the use of IOP-lowering agents to prevent progression of VF defects is reason enough not to consider it. In reality, there are very few randomized controlled trials in neuro-ophthalmology, and many of our interventions are based on our current knowledge of the pathophysiology of disease. Although the data put forth by Grippo et al (8) and Pojda-Wilczek and Wycislo-Gawron (9) are low on the hierarchy of data, both studies do argue for a connection between IOP and VF defects in patients with ODD. Furthermore, after a year of treatment, the patients in the study by Pojda-Wilczek et al showed an improvement in the VF MD and stabilization of the mean rNFL thickness in the treated eye compared with the untreated fellow eye. Finally, the use of the study of Nolan et al (11) to argue against the use of IOP-lowering agents is unwarranted, as this study was cross-sectional and did not follow the patients over time to determine whether VF or mean rNFL changes were affected by IOP (or IOP-lowering) over time. Although the cost of IOP-lowering therapy is significant, in appropriate patients, the cost-benefit ratio is likely to be in favor of preventing loss of vision. In conclusion, I applaud Dr. Falardeau on her arguments, and I agree with most of them. I think we can both agree that further study in this area is necessary. A randomized controlled trial would be helpful and could be feasible given the relatively high prevalence of ODD compared with other neuro-ophthalmic diseases. Until then, the decision to lower IOP in these patients should be made taking into account the patient’s risk factors, age, current VF and mean rNFL parameters, as well as physician and patient goals and expectations. Rebuttal: Julie M. Falardeau, MD Dr. Pineles states that IOP-lowing therapy has been used successfully in the treatment of other optic neuropathies without OHT, such as NTG. Other than glaucomatous optic neuropathy (with or without OHT), I am unaware of any other optic neuropathy where an IOP-lowering agent has proven to be beneficial. I agree with her statement that NTG and ODD are distinct entities and entirely different diseases. Consequently, extrapolation from Normal-Tension Glaucoma studies to justify the use of IOP-lowering agents in ODD seems like a stretch. Falardeau et al: J Neuro-Ophthalmol 2020; 40: 538-543 The study by Grippo et al (8) revealed that visual field loss was significantly associated with OHT in patients with ODD, which raises the possibility of superimposed glaucomatous optic neuropathy. In the case of hypertensive eyes with ODD, the use of an IOP-lowering agent seems appropriate. However, I do not believe that the current literature supports the routine use of IOP-lowering agents in all ODD eyes. Dr. Pineles discusses a recent study by Pojda-Wilczek and Wycislo-Gawron on the effect of a decrease in IOP on optic nerve function in ODD eyes (9). The authors 541 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Point Counter-Point state that their study showed a statistically significant decreased in MD index, increase in PERG N95 amplitude, and RNFL stabilization in normotensive ODD eyes treated with IOP-lowering agent (eye with more severe visual field loss) compared with fellow untreated ODD eye. Consequently, the authors are recommending Brinzolamide therapy in all patients with drusen-associated optic neuropathy. Dr. Pineles provides a nice summary of their results but failed to mention that the authors did not include a section dedicated to the study’s limitations. Among these limitations: (1) the study design is flawed by a selection bias; (2) the data analysis did not include a multivariate model to control for all the baseline factors (demographic factors such as age, gender; ocular factors such as baseline visual field MD, RNFL, PERG) and most importantly (given their hypothesis) the change in IOP; and (3) the visual field data are “noisy” with possible learning effect accounting for the “improvement” in MD index in the treatment group. It is important to mention that the authors state in the Discussion that in individual examinations, there was little improvement of sensitivity and decrease of area of scotomas. Although their findings are interesting, I would be very reluctant to recommend treatment on the basis of PERG N95 results in isolation, especially when no improvement was found with the pattern visual evoked potential. Until we have more studies adhering to more rigorous standards, and demonstrating more robust and reliable effects, the routine use of IOP-lowering agents in normotensive ODD eyes should not be advocated. Conclusions: Andrew G. Lee, MD and Gregory P. Van Stavern, MD There is no high-quality evidence guiding management of patients with optic disc drusen and visual field loss. This type of evidence may quite difficult to obtain, given the mild nature of field loss in most patients and the very slow rate of progression, both of which would entail a large sample size and long duration of follow-up. Use of IOP-lowering agents in patients with ODD and high IOP seems reasonable and supported by evidence. Use of such agents in other patients must be individualized, taking into account patient-specific factors, including baseline VF loss, density of drusen, and rate of progression. REFERENCES 12. Lansche RK, Rucker CW. Progression of defects in visual fields produced by hyaline bodies in optic disks. AMA Arch Ophthalmol. 1957;58:115–121. 13. Saylor M, McLoon LK, Harrison AR, Lee MS. Experimental and clinical evidence for brimonidine as an optic nerve and retinal neuroprotective agent: an evidence-based review. Arch Ophthalmol. 2009;127:402–406. 14. Roh S, Noecker RJ, Schuman JS. Evaluation of coexisting optic nerve head drusen and glaucoma with optical coherence tomography. Ophthalmology. 1997;104:1138–1144. 15. Samples JR, van Buskirk M, Shults WT, Van Dyk HJ. Optic nerve head drusen and glaucoma. Arch Ophthalmol. 1985;103:1678–1680. 16. Hamann S, Malmqvist L, Costello F. Optic disc drusen: understanding an old problem from a new perspective. Acta Ophthalmol. 2018;96:673–684. 17. Lorentzen SE. Drusen of the optic disk: a clinical and genetic study. Acta Ophthalmol (Copenh). 1966;(suppl 90):91–180. 18. Savino PJ, Glaser JS, Rosenberg MA. A clinical analysis of pseudo- papilledema, II: visual field defects. Arch Ophthalmol. 1979;97:71–75. 19. Hoover DL, Robb RM, Petersen RA. Optic disc drusen in children. J Pediatr Ophthalmol Strabismus. 1988;25:191– 195. 20. Chang MY, Pineles SL. Optic disk drusen in children. Surv Ophthalmol. 2016;61:745–758. 21. Noval S, Visa J, Contreras I. Visual field defects due to optic disk drusen in children. Graefes Arch Clin Exp Ophthalmol. 2013;251:2445–2450. 22. Shelton J, Digre K, Warner J, Katz B. Progression of Visual Field Defects in Patients with Optic Nerve Drusen: Follow-Up With Automated Perimetry. Poster presented at: North American Neuro-Ophthalmology Society meeting (abstract #6); February 7 2011; Vancouver, British Columbia, Canada. 23. Lee AG, Zimmerman MB. The rate of visual field loss in optic nerve head drusen. Am J Ophthalmol. 2005;139:1062–1066. 1. Auw-Haedrich C, Staubach F, Witschel H. Optic disk drusen. Surv Ophthalmol. 2002;47:515–532. 2. Wilkins JM, Pomeranz HD. Visual manifestations of visible and buried optic disc drusen. J Neuroophthalmol. 2004;24:125– 129. 3. Mustonen E. Pseudopapilloedema with and without verified optic disc drusen. A clinical analysis II: visual fields. Acta Ophthalmol (Copenh). 1983;61:1057–1066. 4. Pietruschka G, Priess G. Clinical importance and prognosis of drusen of the disc [in German]. Klin Monbl Augenheilkd. 1973;162:331–341. 5. Killer HE, Pircher A. Normal tension glaucoma: review of current understanding and mechanisms of the pathogenesis. Eye (Lond). 2018;32:924–930. 6. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Collaborative NormalTension Glaucoma Study Group. Am J Ophthalmol. 1998;126:498–505. 7. Abegao Pinto L, Vandewalle E, Marques-Neves C, Stalmans I. Visual field loss in optic disc drusen patients correlates with central retinal artery blood velocity patterns. Acta Ophthalmol. 2014;92:e286–291. 8. Grippo TM, Shihadeh WA, Schargus M, Gramer E, Tello C, Liebmann JM, Ritch R. Optic nerve head drusen and visual field loss in normotensive and hypertensive eyes. J Glaucoma. 2008;17:100–104. 9. Pojda-Wilczek D, Wycislo-Gawron P. The effect of a decrease in intraocular pressure on optic nerve function in patients with optic nerve drusen. Ophthalmic Res. 2019;61:153–158. 10. Schargus M, Gramer E. Optic disc drusen [in German]. Ophthalmologe. 2008;105:693–710. 11. Nolan KW, Lee MS, Jalalizadeh RA, Firl KC, Van Stavern GP, McClelland CM. Optic nerve head drusen: the relationship between intraocular pressure and optic nerve structure and function. J Neuroophthalmol. 2018;38:147–150. 542 Falardeau et al: J Neuro-Ophthalmol 2020; 40: 538-543 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Point Counter-Point 24. Malmqvist L, Wegener M, Sander BA, Hamann S. Peripapillary retinal nerve fiver thickness corresponds to drusen location and extent of visual field defects in superficial and buried optic disc drusen. J Neuroophthalmol. 2016;36:41–45. 25. Malmqvist L, Lund-Andersen H, Hamann S. Long-term evolution of superficial optic disc drusen. Acta Ophthalmol. 2016;96:352–356. 26. Coleman AL, Miglior S. Risk factors for glaucoma onset and progression. Surv Ophthalmol. 2008;53(suppl 1):S3–S10. Falardeau et al: J Neuro-Ophthalmol 2020; 40: 538-543 27. Sena DF, Lindskey K. Neuroprotection for treatment of glaucoma in adults. Cochrane Database Syst Rev. 2017:CD006539. 28. Stewart WC, Stewart JA, Nasser OJ, Mychaskiw MA. Costeffectiveness of treating ocular hypertension. Ophthalmology. 2008;115:94–98. 29. Newman-Casey PA, Woodward MA, Niziol LM, Lee PP, De Lott LB. Brand medications and medicate part D. Ophthalmology. 2018;125:332–339. 543 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.