Consensus guidelines on GA diagnosis and management

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Reviewed by Carl R. Regillo, MD

With the current focus on stopping the progression to geographic atrophy (GA) associated with age-related macular degeneration (AMD), physicians and researchers are fine-tuning the identification of the various disease stages, management scenarios, and treatment considerations for this patient population.

Carl Regillo, MD, from Mid Atlantic Retina, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, was the first author of a report issued by an expert panel of optometrists, comprehensive ophthalmologists, and retina specialists, and published in Clinical Ophthalmology.¹

“Early identification of GA will lead to optimal patient outcomes, while a standardized management scenario will reduce clinical burden among eye care providers treating patients with GA,” the authors commented.

The panel met virtually for a roundtable discussion to create consensus guidelines on GA management. The discussion centered on identifying GA using various imaging modalities, collaborative referral strategies, and optimal disease management. A previous online survey gathered information regarding the greatest unmet needs in GA treatment and how best to overcome them.

Roundtable recommendations

The key takeaways were as follows:

• Early identification/diagnosis of GA are paramount for optimal patient outcomes, strengthening the rationale for needing more complete recommendations on disease identification, timely referral, and treatment of patients with GA.
• Early identification of GA by non-retina specialists will decrease rates of missed diagnoses and may help mitigate disease complications and related comorbidities, ultimately improving visual outcomes.
• Anterior-segment specialists should be able to identify GA to help improve patient expectations following cataract surgery, as it may be associated with an increased risk of AMD progression.²

GA imaging

A number of imaging modalities can detect GA, but OCT is preferred for its ease of use and greater accessibility to optometrists and ophthalmologists. The OCT B-scan provides a cross-sectional macular image facilitating rapid and noninvasive assessment of the inner and outer photoreceptors, retinal pigment epithelium (RPE), Bruch’s membrane, and choroid.

To identify and diagnose GA earlier, recognition of specific hallmarks of early/intermediate AMD on OCT images is mandatory; drusen are generally wavy, dome-shaped, triangular, or sawtooth-like disruptions under the neurosensory retina.^3,4 Irregularities vary in size and reflective intensity. Clinicians should focus on the RPE level, especially during early-stage disease when abnormalities may not be particularly evident.

Lesions possibly associated with a high risk of developing GA include hyperreflective foci and drusen volume. Reticular pseudodrusen between the RPE and inner segment/outer segment junction represent a risk for AMD progression.⁵ On OCT, they appear as hyperreflective material above the RPE, unlike regular drusen below the RPE.⁶

Incomplete RPE and outer retinal atrophy (iRORA), other high-risk signs, appear on OCT as hypertransmission into the choroid with a corresponding zone of attenuation/disruption of the RPE and evidence of overlying photoreceptor degeneration that does not meet the complete RPE and outer retinal atrophy (cRORA) criteria.⁷

With progression, OCT visualizes hypertransmission beyond atrophic lesions resulting from increased light transmission into the choroid with loss of the RPE. The GA location/extent may vary considerably. Similar to iRORA in the near-preceding stages of AMD-related GA, cRORA indicates the presence of GA.⁸ On OCT, cRORA also specifically refers to hypertransmission of at least 250 µm in diameter with a zone of attenuation or disruption of the RPE of at least 250 µm in diameter with evidence of overlying photoreceptor degeneration and no scrolled RPE or signs of an RPE tear.

En-face OCT images, which facilitate viewing the total GA lesion area, pinpoint lesion location with respect to the fovea and disease unifocality or multifocality.

Fundus autofluorescence (FAF), used less to identify early/intermediate AMD, does not provide much additional information compared to OCT and is difficult for patients because of the high light intensity during image acquisition.²

GA lesions appear as areas of hypoautofluorescence due to a lack of lipofuscin from RPE cell atrophy. FAF also visualizes the total GA lesion area, focality characteristics, provides information concerning its location relative to the fovea., and identifies specific lesion characteristics through distinct hyperautofluorescence patterns along lesion borders, which may predict the GA progression rate.^9,10 Since the fovea appears hypoautofluorescent, determining the GA location is difficult on FAF.

Managing and treating GA

The expert panel described considerations about collaborative care for referral and follow-up scenarios to optimize diagnosis and management.

Preemptive scans can be obtained during routine eye care to catch AMD early. Patients with early AMD can be followed annually and with intermediate AMD every 6 months. Patients can self-monitor using the Amsler grid or preferential hyperacuity perimetry home testing between visits. Physicians may suggest dietary/lifestyle counseling and use of vitamin/mineral supplements.

A nonurgent referral to a retina specialist is recommended for suspected GA. Suspected neovascular AMD (nAMD) is more urgent. Consultation with a retina specialist may be considered for patients with intermediate AMD if recent visual changes or ophthalmic surgery were mentioned. “All eye care providers should be adept at identifying the various AMD stages and forms,” the panelists stated.

The severity and progression rates vary from patient to patient, mandating changes in follow-up frequency based on signs of increased risk and patient monocularity. Timing of referrals to retina specialists must be optimized to consider the burden on patients and caregivers and practice volume and location.

GA treatment by retina specialists should be personalized maximize quality of life. Treatment or monitoring by a comprehensive ophthalmologist under the guidance of a retina specialist can streamline care and maintain compliance. The treatment frequency should balance the safety and efficacy and the patient and provider burden.

Current anti-complement therapy for GA requires office visits every 1 to 2 months. The recommended dosing for intravitreal avacincaptad pegol (Izervay, Iveric Bio) is 2 mg (0.1 mL of 20 mg/mL solution) for each affected eye once monthly (~28 ± 7 days) for up to 12 months, and that for intravitreal pegcetacoplan (Syfovre, Apellis Pharmaceuticals) is 15 mg (0.1 mL of 150 mg/mL solution) for each affected eye once every 25-60 days.^11,12

Lesion size, location, and characteristics such as perilesional hyperautofluoresence affect which eyes with GA may benefit from treatment and treatment frequency. Extrafoveal GA lesions progress more rapidly than foveal lesions,¹⁰ underscoring the importance of early intervention.

However, individualization of GA treatment may affect an ophthalmologist’s decision to treat. GA may develop bilaterally in up to 65% of cases,¹³ and treatment of one or both eyes must be considered. “Generally, treatment decisions are determined by symptoms, visual acuity, age, fellow-eye status, ocular comorbidities, and the discretion of the physician and patient to conduct a comprehensive personalized risk-benefit assessment is guided by a general evidence-based treatment algorithm,” the panelists commented. Patient education about GA progression and treatment expectations is important.

nAMD and GA, late stages of the same disease, can co-exist. If nAMD develops during GA treatment, nAMD treatment should start if there are signs of macular exudation. Some type 1, non-exudative choroidal neovascularization lesions may not require immediate treatment but should be followed closely for progression. Ongoing treatment of GA in the eye that develops choroidal neovascularization and requires anti-vascular endothelial growth factor therapy is at the discretion of the managing physician and patient. Combined GA and nAMD treatment is feasible and safe, but injections may need to be administered on different clinical visits or separated by about 30 minutes on the same day to minimize the risk of excessive intraocular pressure elevation.

Severe adverse events, ie, endophthalmitis, ischemic optic neuropathy, sustained elevated intraocular pressure, and significant, nontransient intraocular inflammation, may warrant cessation of GA treatment, especially if associated with retinal/occlusive vasculitis.

Severe central vision loss may represent a scenario in which ongoing treatment risks/burdens may not outweigh any potential benefits. A detailed clinical examination before treatment may lessen potential adverse events. Treating physician should educate patients about symptoms that signify adverse events, e.g., pain, new visual changes, or new floaters. Finally, if patient compliance significantly negatively affects the treatment regimen, discontinuation may be considered.

Approved and emerging GA treatments will cause a paradigm shift in the identification and management of GA, resulting in additional or new considerations regarding optimal patient care. The panel agreed that because current GA treatments slow but do not stop GA progression, and early identification of GA is important to ensure that patients with this advanced form of dry AMD have the best possible outcomes. Early intervention may lead to a reduction in the rate of vision loss and improvements in overall quality of life. Despite GA being a retinal disease, panelists believe the availability of GA treatment will affect all optometrists, comprehensive ophthalmologists, and retina specialists. It is imperative that all eye care providers have disease knowledge about GA and understand best practices for GA identification and how to collaborate with other ECPs to optimize multidisciplinary patient care, the authors concluded.

References

1. Regillo CD, Nijm LM, Shechtman DL, et al. Considerations for the identification and management of geographic atrophy: recommendations from an expert panel. Clin Ophthalmol. 2024;18:325–335; published online Feb 2, 2024; doi: 10.2147/OPTH.S445755

2. Armenti ST, Greenberg JP, Smith RT. Quantitative fundus autofluorescence for the evaluation of retinal diseases. J Vis Exp. 2016;109:53577. doi: 10.3791/53577

3. Drusen characterization with multimodal imaging - PMC. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952278/. Accessed June 27, 2023.

4. Schmidt-Erfurth U, Klimscha S, Waldstein SM, Bogunović H. A view of the current and future role of optical coherence tomography in the management of age-related macular degeneration. Eye. 2017;31:26–44. doi: 10.1038/eye.2016.227

5. Klein R, Meuer SM, Knudtson MD, Iyengar SK, Klein BEK. The epidemiology of retinal reticular drusen. Am J Ophthalmol. 2008;145:317–326. doi: 10.1016/j.ajo.2007.09.008

6. Querques G, Canouï-Poitrine F, Coscas F, et al. Analysis of progression of reticular pseudodrusen by spectral domain–optical coherence tomography. Invest Ophthalmol Visual Sci. 2012;53:1264–1270. doi: 10.1167/iovs.11-9063

7. Guymer RH, Rosenfeld PJ, Curcio CA, et al. Incomplete retinal pigment epithelial and outer retinal atrophy in age-related macular degeneration. Ophthalmology. 2020;127:394–409. doi: 10.1016/j.ophtha.2019.09.035

8. Sadda SR, Guymer R, Holz FG, et al. Consensus definition for atrophy associated with age-related macular degeneration on OCT: classification of atrophy report 3. Ophthalmology. 2018;125:537–548. doi: 10.1016/j.ophtha.2017.09.028

9. Holz FG, Strauss EC, Schmitz-Valckenberg S, van Lookeren Campagne M. Geographic atrophy: clinical features and potential therapeutic approaches. Ophthalmology. 2014;121:1079–1091. doi: 10.1016/j.ophtha.2013.11.023

10. Fleckenstein M, Mitchell P, Freund KB, et al. The progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology. 2018;125:369–390. doi: 10.1016/j.ophtha.2017.08.038 [PubMed] [CrossRef] [Google Scholar]

11. IVERIC bio, Inc. IZERVAY - avacincaptad pegol injection. Prescribing Information. Available from: https://ivericbio.com/wp-content/uploads/IZERVAY-avacincaptad-pegol-intravitreal-solution-PI_Final_8.4.23.pdf. Accessed December 13, 2023.

12. Apellis Pharmaceuticals, Inc. SYFOVRE- pegcetacoplan injection, solution. Prescribing Information. Available from: https://pi.apellis.com/files/PI_SYFOVRE.pdf. Accessed December 13, 2023.

13. Lindblad AS, Lloyd PC, Clemons TE, et al. Change in area of geographic atrophy in the Age-Related Eye Disease Study: AREDS report number 26. Arch Ophthalmol. 2009;127:1168–1174. doi: 10.1001/archophthalmol.2009.198