Radiation retinopathy intricacies and advances in management

Figures & data

Table 1. Radiation dose effects on ocular structures

Radiation dose (cGy)	Affected ocular structure	Comments
>50	Lens: Cataract changes (ICRP threshold)^Citation32–34	Six-fold increase in cataract extraction rates after ≥ 500 cGy compared to eyes exposed to ≤ 250 cGy.^Citation35 Lens-sparing techniques upon irradiation can reduce the cataract formation rate from 87.5% to 23.1%.^Citation36
3000–4000 (and large fractions eg, 1000 cGy)	Eyelid erythema, blepharitis, and lash loss^Citation37 Cornea: Keratitis, edema, and small ulcers^Citation37	Alterations prevented with smaller fractions until the threshold exceeds 5000 cGy^Citation37
>5000-6000	Lacrimal gland changes, tear duct atrophy, ocular surface disease→keratoconjunctivitis sicca and permanent loss of secretions→corneal ulceration (late complication)^Citation32,Citation37,Citation38	≤ 4000 cGy could avoid development of dry eyes^Citation32,Citation38

Abbreviations: cGy, centigray; ICRP, International Commission on Radiological Protection

Table 2. Studies on several treatment regimens using intravitreal anti-VEGF injections for radiation retinopathy

Treatment options	Regimen	Results	Follow-up period (months)
Bevacizumab	Fixed monthly^Citation96	VA: 42% increased BCVA, 44% stable BCVA CMT: 56% decreased CMT, 31% stable CMT *Benefits from monthly injections. Extending the interval beyond 4 weeks may worsen edema, caution advised.	4–6
	Loading (3 monthly high-dose injections)^Citation98	VA: Baseline 0.55 logMAR to 0.51 logMAR CMT: Baseline 406 μm to 395 μm *Patients with persistent retinopathy who do not respond to standard-dose bevacizumab have limited benefits from high-dose treatments. Improvement in the VA and macular thickness was only significant in about 30% of patients.	9
	Loading (3 initial monthly) then PRN^Citation132	VA: Baseline 0.7 logMAR to 1.3 logMAR (Loss of ~5 lines) CFT: Baseline 340 μm to 353 μm *Benefits from injections every 90 days or sooner.	19
Bevacizumab or ranibizumab	Fixed bimonthly^Citation133	VA: Baseline 0.44 logMAR to 0.52 logMAR CMT: Baseline 304 μm to 285 μm FAZ area: Baseline 0.62 to 1.02 *Significant reduction in BCVA loss and FAZ enlargement under the 2-month interval.	6
	Every 4–12 weekly^Citation131	VA: Baseline 69% with 20/40 or better to 65% at last treatment examination, baseline 30% with 20/200 or better but worse than 20/40 to 31% at last examination. Probability of remaining within 2 lines of initial VA after anti-VEGF: 69% at 5 yrs and 38% at 8 years. CFT: Baseline 364.9 μm to 288 μm at 2 years to 382.8 μm at 4 years *Constant anti-VEGF administration over 10 years was well tolerated, preserved vision, and suppressed macular edema although edema may re-emerge after several years of treatment.	81
Aflibercept	Monthly then PRN^Citation117	VA: Baseline 0.9 logMAR to 0.55 logMAR at 12 m and 0.56 logMAR at 24 m (mean gain of 17 ETDRS letters) CFT: Baseline 546 μm to 245 μm at 12 m to 223 μm at 24 m Marked improvement in the radiation maculopathy stage *Aflibercept allows both functional and anatomic improvements with a low number of injections.	24
	Fixed, every 6 weeks, vs variable, treat and adjust centering on 6 weeks^Citation134	VA: Baseline 20/63 to 20/62 (42.5% eyes with better than 20/50 BCVA, only 5% with worse than 20/200 BCVA) CMT: Baseline 432 μm to 294 μm *No difference between groups, unable to extend treatments beyond 6 weeks, ongoing treatment required	12
Ranibizumab	Loading (3 initial monthly) then PRN stopped at 6 months^Citation104	VA: Baseline 0.58 logMAR to 0.38 logMAR at 6 m to 0.75 logMAR at 12 m CFT: Baseline 478 μm to 387 μm at 6 m and 509 μm at 12 m *Ranibizumab superior to laser treatment until 6 months, but benefit disappears if treatment is stopped.	6 and 12
	Fixed, every month vs 3 initial monthly then PRN^Citation135	VA: Baseline 56.9 ETDRS letters (gain of 4.0 letters) CMT: Baseline 423.1 μm (mean change of −97.0 μm) Persistent retinal hemorrhage: Baseline 75% of patients to 0% vs VA: Baseline 60.3 ETDRS letters (gain of 0.9 letters) CMT: Baseline 388.2 μm (mean change of −71.0 μm) Persistent retinal hemorrhage: Baseline 87.5% of patients to 12.5% *Increased effectiveness seen in the fixed, monthly regimen than the PRN approach; concomitant laser did not add benefits	12

Abbreviations: BCVA: Best-corrected visual acuity; CFT: Central foveal thickness; CMT: Central macular thickness; FAZ: Foveal avascular zone; PRN: Pro-re-nata; VA: Visual acuity

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