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Retrobulbar radiation, optic disc cupping, and neuroretinal rim thinning

Published:April 24, 2022DOI:https://doi.org/10.1016/j.jcjo.2022.03.010
      Dear Editor,
      Thank you for the opportunity to respond to Drs. Dalvin and Roddy's letter to the editor regarding our recently published original observations describing “Optic disc cupping after circumpapillary Pd-103 slotted plaque radiation therapy.”
      • Finger PT
      • Fam A
      • Tomar AS
      • Radcliffe NM.
      Optic disc cupping after circumpapillary Pd-103 slotted plaque radiation therapy.
      They point out that their recently published article in the Journal of Neuroophthalmology noted, “Post radiation optic atrophy is associated with intraocular pressure and may manifest with neuroretinal rim thinning.”2 We read their article (which was published within 30 days of ours) with great interest. They reported that their posteriorly placed radiation plaques resulted in either no optic neuropathy, or optic neuropathy without neuroretinal thinning or 19.2% with neuroretinal thinning (Table 1). In contrast, in our study, plaque therapy resulted in 88.5% with optic disc cupping.
      • Finger PT
      • Fam A
      • Tomar AS
      • Radcliffe NM.
      Optic disc cupping after circumpapillary Pd-103 slotted plaque radiation therapy.
      Let's closely examine some of the differences between these two studies.
      Table 1Comparison of study methods and outcomes
      Study# of PatientsPosition Tumor/PlaquePlaque COMS - ShellRadionuclide Seed-SourceOptic Disc Radiation Dose (mean)Disc CuppingDisc PallorIOP IncreasedOCT-ATTT- addedEnucleation Secondary
      Galvin et. al.
      • Dalvin LA
      • Deufel CL
      • Corbin KS
      • Petersen IA
      • Olsen TW
      • Roddy GW.
      Postradiation optic atrophy is associated with intraocular pressure and may manifest with neuroretinal rim thinning.
      78< 6 mm to discRoundiodine-12584 Gy19.2% (n = 15)YesYesNo(n = 4/15, 27%)
      This is the percentage of the 19.2% noted to exhibit neuroretinal thinning.
      3
      Finger et. al.
      • Finger PT
      • Fam A
      • Tomar AS
      • Radcliffe NM.
      Optic disc cupping after circumpapillary Pd-103 slotted plaque radiation therapy.
      39< 1.5 mm, juxta, circumpapillary8-mm Slotted
      See technique, all slots are 8 mm wide whereas slot depth depends on the distance required to circumnavigate the melanoma and margin. 6.
      palladium-103113 Gy88.5% (n = 35)NoNoYesNoneNone
      COMS, Collaborative Ocular Melanoma Study; IOP, intraocular pressure; OCT-A, optical coherence tomography-angiography; TTT, transpupillary thermotherapy; juxta, juxtapapillary, completely encircling and/or covering the optic disc; Gy, Gray
      low asterisk This is the percentage of the 19.2% noted to exhibit neuroretinal thinning.
      # See technique, all slots are 8 mm wide whereas slot depth depends on the distance required to circumnavigate the melanoma and margin. 6.
      The tumors selected and methods of treatment were quite different.
      • Finger PT
      • Fam A
      • Tomar AS
      • Radcliffe NM.
      Optic disc cupping after circumpapillary Pd-103 slotted plaque radiation therapy.
      ,
      • Dalvin LA
      • Deufel CL
      • Corbin KS
      • Petersen IA
      • Olsen TW
      • Roddy GW.
      Postradiation optic atrophy is associated with intraocular pressure and may manifest with neuroretinal rim thinning.
      For example, in Finger et al., we selected only peripapillary, juxtapapillary, and circumpapillary tumors. Due to their peripapillary location, treatment required 8 mm wide, variable-depth slots to be cut away from standard Collaborative Ocular Melanoma Study plaques to accommodate the retrobulbar optic nerve sheath within the plaque (thereby overcoming its obstruction).
      • Finger PT
      • Fam A
      • Tomar AS
      • Radcliffe NM.
      Optic disc cupping after circumpapillary Pd-103 slotted plaque radiation therapy.
      These plaques covered the entire tumor plus a margin of normal-appearing tissue around the melanoma (American Brachytherapy Society [ABS] “normal” plaque position).
      American Brachytherapy Society - Ophthalmic Oncology Task Force. Electronic address: [email protected]; ABS – OOTF Committee
      The American Brachytherapy Society consensus guidelines for plaque brachytherapy of uveal melanoma and retinoblastoma.
      As a result, Finger's Slots uniquely allowed the plaques to be seated on the posterior pole to directly irradiate most or all of the posterior ocular circulation located immediately beneath the plaque.
      In contrast, Dalvin and Roddy's tumors were selected to be within 6 mm of the optic disc.
      • Dalvin LA
      • Deufel CL
      • Corbin KS
      • Petersen IA
      • Olsen TW
      • Roddy GW.
      Postradiation optic atrophy is associated with intraocular pressure and may manifest with neuroretinal rim thinning.
      It is unlikely that many tumors were juxtapapillary, peripapillary, or circumpapillary because most centers prefer not to treat them with the round Collaborative Ocular Melanoma Study plaques used in their study. In that the optic nerve sheath diameter extends 1.5 mm beyond the intraocular edge of the optic disc, there is no anatomical chance Dalvin and Roddy's round plaques could have achieved ABS “normal” plaque position, much less be seated over most or all the papillary and peripapillary circulation.
      Studies have revealed, however, that round juxtaneural plaques tilt along their posterior extent and thus spray radiation in the direction of the posterior, typically uncovered melanoma and (of interest for this comparison) the neural and perineural circulation.
      American Brachytherapy Society - Ophthalmic Oncology Task Force. Electronic address: [email protected]; ABS – OOTF Committee
      The American Brachytherapy Society consensus guidelines for plaque brachytherapy of uveal melanoma and retinoblastoma.
      ,
      • Studenski MT
      • Markoe A
      • Samuels SE
      • Correa ZM
      • Bossart E
      • Harbour JW.
      Comprehensive assessment of the effect of eye plaque tilt on tumor dosimetry.
      The use of plaque-tilt during radiation therapy challenges a medical physicists' ability to determine the actual dose to the optic nerve and emissary blood vessels. Dalvin and Roddy were likely considering this when adding transpupillary thermotherapy (TTT) at the time of plaque removal for 23 eyes (Table 1).
      • Dalvin LA
      • Deufel CL
      • Corbin KS
      • Petersen IA
      • Olsen TW
      • Roddy GW.
      Postradiation optic atrophy is associated with intraocular pressure and may manifest with neuroretinal rim thinning.
      Clearly, the fact that TTT was used on 27% of the 15 nerves that went on to develop neuroretinal thinning is a confounding factor.
      • Dalvin LA
      • Deufel CL
      • Corbin KS
      • Petersen IA
      • Olsen TW
      • Roddy GW.
      Postradiation optic atrophy is associated with intraocular pressure and may manifest with neuroretinal rim thinning.
      Failure of local tumor control adds further evidence of plaque decentration seen with their approach. Though no reason was given, we noticed that three of their eyes came to enucleation (Table 1).
      • Dalvin LA
      • Deufel CL
      • Corbin KS
      • Petersen IA
      • Olsen TW
      • Roddy GW.
      Postradiation optic atrophy is associated with intraocular pressure and may manifest with neuroretinal rim thinning.
      In contrast, in that Finger's slotted plaque technique allowed for “ABS normal” plaque positioning, there was no need to treat uncovered tumor margins with adjuvant peripapillary TTT, and there were no failures of local control.
      • Finger PT
      • Fam A
      • Tomar AS
      • Radcliffe NM.
      Optic disc cupping after circumpapillary Pd-103 slotted plaque radiation therapy.
      ,
      • Badiyan SN
      • Rao RC
      • Apicelli AJ
      • Acharya S
      • Verma V
      • Garsa AA
      • et al.
      Outcomes of iodine-125 plaque brachytherapy for uveal melanoma with intraoperative ultrasonography and supplemental transpupillary thermotherapy.
      • Maheshwari A
      • Finger PT.
      A 12-year study of slotted palladium-103 plaque radiation therapy for choroidal melanoma: near, touching, or surrounding the optic nerve.
      Our study does not suggest that neuroretinal rim thinning is unique to slotted plaque brachytherapy. Our research revealed a phenomenon where radiation was delivered directly to the papillary and peripapillary vasculature, which resulted in a greater incidence of optic nerve cupping (88.5%) versus (19.2%) neuroretinal thinning observed by Dalvin and Roddy (Table 1). We appreciate, however, that Dalvin and Roddy's research offers supporting evidence that neuroretinal rim thinning may occur with high radiation doses to the perineural circulation—and not simply in the setting of slotted plaques.
      Lastly, Dalvin and Roddy suggest that radiation-induced optic nerve vasculopathy may have made the optic nerve head more sensitive to slight increases or even normal intraocular pressures. Though we did not find any raised intraocular pressure in our study, we agree this is certainly a theory worth investigating.
      In summary, significant methodologic differences exist between the two studies that affect their relative ability to offer proof that radiation can induce optic nerve cupping.
      • Finger PT
      • Fam A
      • Tomar AS
      • Radcliffe NM.
      Optic disc cupping after circumpapillary Pd-103 slotted plaque radiation therapy.
      ,
      • Dalvin LA
      • Deufel CL
      • Corbin KS
      • Petersen IA
      • Olsen TW
      • Roddy GW.
      Postradiation optic atrophy is associated with intraocular pressure and may manifest with neuroretinal rim thinning.
      Specifically, our study is the only one where quantifiable and reproducible measures of radiation were placed to cover the posterior neural and perineural circulation of the eye.
      • Finger PT
      • Fam A
      • Tomar AS
      • Radcliffe NM.
      Optic disc cupping after circumpapillary Pd-103 slotted plaque radiation therapy.
      This is reflected by the numbers of patients who later developed progressive (optical coherence tomography-angiography–documented) ischemic radiation vasculopathy at the posterior pole along with secondary optic disc cupping.
      • Finger PT
      • Fam A
      • Tomar AS
      • Radcliffe NM.
      Optic disc cupping after circumpapillary Pd-103 slotted plaque radiation therapy.

      Footnotes and Disclosuretshow

      The authors have no proprietary or commercial interest in any materials discussed in this article.
      Supported by: The Eye Cancer Foundation, Inc. (https://eyecancercure.com)

      References

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        Optic disc cupping after circumpapillary Pd-103 slotted plaque radiation therapy.
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        • Dalvin LA
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        • Markoe A
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        • Harbour JW.
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        • Rao RC
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        Outcomes of iodine-125 plaque brachytherapy for uveal melanoma with intraoperative ultrasonography and supplemental transpupillary thermotherapy.
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