Preserving Visual Acuity: A Compelling 12-Year Case Study of Controlling Neovascular Age-Related Macular Degeneration

doi:10.21203/rs.3.rs-3607256/v1

Download PDF

Case Report

Preserving Visual Acuity: A Compelling 12-Year Case Study of Controlling Neovascular Age-Related Macular Degeneration

https://doi.org/10.21203/rs.3.rs-3607256/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background: In neovascular age-related macular degeneration (nAMD) trials, anti-VEGF injection frequency declines after the first year, while outcomes remain primarily related to the number of injections. To date, there are no documented real-life cases in the literature reporting long-term preservation of best corrected visual acuity (BCVA) for more than 7 years in nAMD.

We present a 12-year follow-up of a real-life case of nAMD where BCVA was preserved.

Case presentation: A 67-year-old Caucasian female presented to our department in June 2010 due to decreased vision in her left eye (LE) within the preceding months. Examination showed a BCVA of 85 letters (L) in the right eye (RE) and 35 L in the LE. Fundus examination showed drusen in the macula of both eyes and macular edema in the LE. A diagnosis of Type 1 choroidal neovascular membrane (CNV) in the RE and Type 2 CNV in the LE was established. She undergone 7 injections within the first year in either eye. The LE had a mean of five injections per year, and the RE had a mean of seven injections per year, from 2010 to 2022. RE's BCVA dropped by 8 L (85 L to 77 L) and central retinal thickness (CRT) increased by 16 μm (276 μm to 292 μm), while LE’s BCVA increased by 28 L (35 L to 63 L) and CRT decreased by 369 μm (680 μm to 311 μm), at the twelfth year.

Conclusions: The number of injections is paramount in preserving BCVA and achieving favorable functional outcomes in nAMD, even after 12 years of treatment.

Neovascular Age-Related Macular Degeneration

visual acuity

pro re nata

treat and extend

number of injections

real-world

Age related macular degeneration (AMD) is the most common cause of blindness after the 7th decade of life in developed countries [1]. Its advanced forms are characterized by choroidal neovascular membrane (CNV) or geographic atrophy. Anti-VEGF agents are the mainstay of the treatment of neovascular AMD (nAMD) [2].

The outcomes are primarily related with the number of injections and not necessarily with the treatment regimen, while the number of injections per year is expected to decrease after the 1st year [3–6]. Unfortunately, the best corrected visual acuity (BCVA) declines with time [7].

Therefore, the objective of this case report is to present a 12-year follow-up of a real-life case of nAMD where BCVA was preserved.

Patient information

A 67-year-old Caucasian female presented to our department in June 2010 due to decreased vision in her left eye (LE) within the preceding months. BCVA was 35 letters (L). The right eye (RE)’s BCVA was 85L. Fundus examination showed drusen in the macula of both eyes and macular edema in the LE.

Diagnostic Assessment

At baseline, optical coherence tomography (OCT) of the LE showed a retinal pigment epithelial detachment (PED) and a hyper-reflective subretinal lesion associated with intraretinal cysts (Fig. 1). RE’s OCT was unremarkable, apart from macular drusen. However, within two months, a nonhomogeneous PED developed along with a discreet amount of subretinal fluid and the presence of intraretinal fluid. A diagnosis of Type 1 CNV in the RE and Type 2 CNV in the LE was established.

Therapeutic Intervention

Therapy began in the LE with five injections, of bevacizumab (three) and ranibizumab (two), in 2010. Treatment of the RE followed, with a total of three injections of ranibizumab in 2010. Within the first year of treatment either eye was treated with 7 injections. The LE had a mean of five injections per year, and the RE had a mean of seven injections per year, from 2010 to 2022. Meanwhile, she underwent cataract surgery on 2021.

Follow-up and Outcomes

The LE improved up to 38 L (+ 3 L) in six months (Fig. 2) and reached a plateau after the first five years of treatment, up to 58L (+ 23 L from baseline, Fig. 2), with a mean of five injections per year (Fig. 3). Nevertheless, in year eleven, there has been a significant decrease in the BCVA related to cataract (Fig. 2). After cataract removal LE’s final BCVA was 63L (+ 28 L from baseline). The LE’s mean central retinal thickness (CRT) decreased from 680 µm to 483 µm during the first year of treatment and continued to show a significant decrease, followed by a continued reduction until year six, to its minimum of 311 µm (Fig. 4). The LE underwent a total of 62 injections in 12 years, 12 of bevacizumab, 15 of ranibizumab and 35 of aflibercept (Fig. 3). Overall, LE’s BCVA increased 28 L (from baseline 35 L to 63 L in year 12) and CRT decreased 369 µm (from 680 µm at presentation to 311 µm in year twelfth).

Conversely, the BCVA of the RE initially declined (during the first two years), from baseline 85 L to 67 L (Fig. 2). Thereafter, a plateau was reached between 70 and 75 L. On 2021, there was a sudden drop to 58 L, followed by a quick recovery (Fig. 2), related to cataract and cataract surgery (Fig. 3). The CRT was not well controlled during the first two years of treatment and showed a late relapse at year five. However, it remained stable afterwards (Fig. 4). The RE received a mean of 7 injections per year, with a total of 91 injections, 35 of ranibizumab and 56 of aflibercept (Fig. 3). RE’s BCVA dropped 8 L along the 12-year timeline, to the end of 2022 (85 L to 77 L, Fig. 2). The difference in CRT along the 12-year timeline was 16 µm (baseline 276 µm to 292 µm in the twelfth year, Fig. 4).

This case report presents a 12-year follow-up of a patient with nAMD who recovered BCVA from the worst eye (+ 28 L, LE 63L) and kept driving vision in the best eye (-8 L, RE 77L), with a mean of 7 injections per year in the RE and 5 injections in the LE. Data from this study support the findings that baseline BCVA is the paramount prognostic factor for the final BCVA, in nAMD. The compliance of the patient was excellent, our department has a system of calling back missing patients and our team did not stop the intravitreal treatments during the COVID pandemic at all [8].

Along the timeline we started with a pro re nata (PRN) protocol, changed for treat and extend (T&E) in 2016 and adopted a fixed protocol in 2020 with more injections in the first semester of the first year than in the second [8]. Since the adjustments of the T&E regimen are based in the presence or absence of relapses, it is not surprising that intra-retinal or subretinal fluid is present in OCT scans until 2019 (Fig. 1). Noteworthy, injections were more frequent in the first year, since the LE had 5 injections in 2010, starting in June and the RE had 3 injections, starting in late August 2010. In 2011 numbers climbed to 7 injections in the LE and 9 injections in the RE (Fig. 3). It is well known that the outcomes are primarily related to the number of injections and these numbers are not far from the “magic” number of 8 injections in the first year [3–5, 8]. Moreover, the fixed regimen decreased the number of required visits from 8 to 2 visits per year, since the OCT scan was always made in the same day of injection [6, 8].

It is known that nAMD treatment results fall short from the desired, either in reported series and Medicare claims data, [5]. We think that the fixed approach based on the number of injections, OCT on the day of injection and a protocol of calling back missing patients may help to improve the final results in a considerable number of patients. The fixed regimen has a minimum number of injections per year and allows, if necessary, an extra injection at any time. Additionally, it spares a lot of visits if the OCT scan is made at the day of injection, from 15 to 4 within a 2-year period [6, 8].

Our study has limitations. Most prominently, it is a case report and the results cannot be extrapolated. Nevertheless, it might have an exploratory value. The fixed protocols may have similar or better results than the PRN or T&E approaches, with a slight trend to overtreatment, albeit with fewer visits. The approaches of the newer drugs seem to encourage the fixed approach [9, 10].

In conclusion, a fixed approach is not reactive, since it is not based on relapses and it consistently stands on the best evidence for treatment outcomes in nAMD, wich is the number of injection given.

Author Contributions

RT and AC contributed equally to this work. RT and NO collected the data. RT, AC and NO were involved in the concept, design, analysis, interpretation of data. RT and AC equally contributed in the drafing of the manuscript. AC was involved in the review of the manuscript. PS contributed to the criation of the figures 2,3 and 4. JS approved the final version to be published. All authors reviewed and accepted the manuscript.

Ethical approval and consent to participate

Need for approval from ethics was waived.

Availability of data and materials

The data is accessible through Retina.PT, a platform hosted on the website https://www.ger-portugal.com/. However, since accessing the data requires an account login, the datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Consent for publication

Informed consent to publish this case report in an online publication has been obtained from the patient, including for images.

Competing interests

All authors declare that they have no competing interests.

Funding

None.

Flaxel CJ, Adelman RA, Bailey ST, Fawzi A, Lim JI, Vemulakonda GA, et al. Age-Related Macular Degeneration Preferred Practice Pattern®. Ophthalmology. 2020;127(1):P1-p65.
Pencak M, Veith M. Asymmetric response to ranibizumab in mixed choroidal neovascularization in a neovascular age-related macular degeneration diagnosed on OCT angiography - case report. BMC Ophthalmol. 2021;21(1):42.
Wecker T, Grundel B, Reichl S, Stech M, Lange C, Agostini H, et al. Anti-VEGF injection frequency correlates with visual acuity outcomes in pro re nata neovascular AMD treatment. Sci Rep. 2019;9(1):3301.
Holz FG, Tadayoni R, Beatty S, Berger A, Cereda MG, Cortez R, et al. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. British Journal of Ophthalmology. 2015;99(2):220-6.
Spaide RF. Antivascular endothelial growth factor dosing and expected acuity outcome at 1 year. Retina. 2021;41(6):1153-63.
Arnold JJ, Campain A, Barthelmes D, Simpson JM, Guymer RH, Hunyor AP, et al. Two-year outcomes of "treat and extend" intravitreal therapy for neovascular age-related macular degeneration. Ophthalmology. 2015;122(6):1212-9.
Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR, Zhang K. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology. 2013;120(11):2292-9.
Campos A, Oliveira N, Martins J, Arruda H, Sousa J. The Paradigm Shift of Ophthalmology in the COVID-19 Era. Clinical ophthalmology. 2020;14:2625-30.
Heier JS, Khanani AM, Quezada Ruiz C, Basu K, Ferrone PJ, Brittain C, et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. Lancet. 2022;399(10326):729-40.
Wykoff CC, Brown DM, Reed K, Berliner AJ, Gerstenblith AT, Breazna A, et al. Effect of High-Dose Intravitreal Aflibercept, 8 mg, in Patients With Neovascular Age-Related Macular Degeneration: The Phase 2 CANDELA Randomized Clinical Trial. JAMA ophthalmology. 2023;141(9):834-42.

No competing interests reported.

Download PDF

Editorial decision: Revision requested
01 Jan, 2024
Reviews received at journal
29 Dec, 2023
Reviews received at journal
02 Dec, 2023
Reviewers agreed at journal
26 Nov, 2023
Reviewers invited by journal
26 Nov, 2023
Editor invited by journal
16 Nov, 2023
Editor assigned by journal
16 Nov, 2023
Submission checks completed at journal
16 Nov, 2023
First submitted to journal
13 Nov, 2023

You are reading this latest preprint version

Preserving Visual Acuity: A Compelling 12-Year Case Study of Controlling Neovascular Age-Related Macular Degeneration

Status:

Version 1

Abstract

Figures

Introduction

Case Presentation

Patient information

Diagnostic Assessment

Therapeutic Intervention

Follow-up and Outcomes

Discussion/Conclusion

Declarations

References

Additional Declarations

Status:

Version 1