Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2589_Библиотеки_им_академика_М_И_Перельмана
.pdf
References
https://t.me/medicina_free
391
Ophthalmol Retina. 2022;6(10):914–21. https://doi.
org/10.1016/j.oret.2022.04.012. Epub 2022 Apr 20.
33. Foss A, Rotsos T, Empeslidis T, Chong
V. Development of macular atrophy in
patients with wet age-related macular degeneration receiving anti-VEGF treatment.
Ophthalmologica. 2022;245(3):204–17. https://doi.
org/10.1159/000520171. Epub 2021 Oct 25.
34. Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR,
Zhang K, SEVEN-UP Study Group. Seven-year
outcomes in ranibizumab-treated patients in
ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology.
2013;120(11):2292–9. https://doi.org/10.1016/j.
ophtha.2013.03.046. Epub 2013 May 3.
35. Takahashi A, Ooto S, Yamashiro K, Tamura
H, Oishi A, Miyata M, Hata M, Yoshikawa M,
Yoshimura N, Tsujikawa A. Pachychoroid geographic atrophy: clinical and genetic characteristics. Ophthalmol Retina. 2018;2(4):295–305.
https://doi.org/10.1016/j.oret.2017.08.016. Epub
2017 Nov 22.
36. Hirabayashi K, Yu HJ, Wakatsuki Y, Marion KM,
Wykoff CC, Sadda SR.OCT risk factors for development of atrophy in eyes with intermediate agerelated macular degeneration Ophthalmol Retina
2022. pii: S2468-6530(22)00486-9. https://doi.
org/10.1016/j.oret.2022.09.007. Epub ahead of print.
37. Agrón E, Domalpally A, Cukras CA, Clemons TE,
Chen Q, Swaroop A, Lu Z, Chew EY, Keenan TDL,
AREDS and AREDS2 Research Groups. Reticular
Pseudodrusen status, ARMS2/HTRA1 genotype,
and geographic atrophy enlargement: age-related
eye disease study 2 report 32. Ophthalmology.
2022. pii: S0161-6420(22)00932-0. doi: https://doi.
org/10.1016/j.ophtha.2022.11.026. Epub ahead of
print.
38. Chakravarthy U, Bailey CC, Scanlon PH, McKibbin
M, Khan RS, Mahmood S, Downey L, Dhingra
N, Brand C, Brittain CJ, Willis JR, Venerus A,
Muthutantri A, Cantrell RA.Progression from early/
intermediate to advanced forms of age-related macular degeneration in a large UK cohort: rates and
risk factors. Ophthalmol Retina. 2020;4(7):662–72.
https://doi.org/10.1016/j.oret.2020.01.012. Epub
2020 Jan 25.
39. Schmitz-Valckenberg S, Sahel JA, Danis R,
Fleckenstein M, Jaffe GJ, Wolf S, Pruente C, Holz
FG. Natural history of geographic atrophy progression secondary to age-related macular degeneration (geographic atrophy progression study).
Ophthalmology. 2016;123(2):361–8. https://doi.
org/10.1016/j.ophtha.2015.09.036. Epub 2015 Nov
3.
40. Holekamp N, Wykoff CC, Schmitz-Valckenberg
S, Monés J, Souied EH, Lin H, Rabena MD,
Cantrell RA, Henry EC, Tang F, Swaminathan B,
Martin J, Ferrara D, Staurenghi G. Natural history
of geographic atrophy secondary to age-related
macular degeneration: results from the prospective
proxima A and B clinical trials. Ophthalmology.
2020;127(6):769–83. https://doi.org/10.1016/j.oph-
tha.2019.12.009. Epub 2019 Dec 14.
41. Pfau M, von der Emde L, de Sisternes L, Hallak
JA, Leng T, Schmitz-Valckenberg S, Holz FG,
Fleckenstein M, Rubin DL. Progression of photoreceptor degeneration in geographic atrophy secondary to age-related macular degeneration. JAMA
Ophthalmol. 2020;138(10):1026–34. https://doi.
org/10.1001/jamaophthalmol.2020.2914.
42. Agrón E, Mares J, Chew EY, Keenan TDL, AREDS2
Research Group. Adherence to a Mediterranean
diet and geographic atrophy enlargement rate: agerelated eye disease study 2 report 29. Ophthalmol
Retina. 2022;6(9):762–70. https://doi.org/10.1016/j.
oret.2022.03.022. Epub 2022 Apr 4.
43. Fleckenstein M, Keenan TDL, Guymer RH,
Chakravarthy U, Schmitz-Valckenberg S, Klaver
CC, Wong WT, Chew EY. Age-related macular
degeneration. Nat Rev Dis Primers. 2021;7(1):31.
https://doi.org/10.1038/s41572- 021- 00265- 2.
44. Holz FG, Sadda SR, Busbee B, Chew EY, Mitchell
P, Tufail A, Brittain C, Ferrara D, Gray S, Honigberg
L, Martin J, Tong B, Ehrlich JS, Bressler NM,
Chroma and Spectri Study Investigators. Efcacy
and safety of lampalizumab for geographic atrophy
due to age-related macular degeneration: chroma
and spectri phase 3 randomized clinical trials.
JAMA Ophthalmol. 2018;136(6):666–77. https://
doi.org/10.1001/jamaophthalmol.2018.1544.
45. Liao DS, Grossi FV, El Mehdi D, Gerber MR,
Brown DM, Heier JS, Wykoff CC, Singerman LJ,
Abraham P, Grassmann F, Nuernberg P, Weber
BHF, Deschatelets P, Kim RY, Chung CY, Ribeiro
RM, Hamdani M, Rosenfeld PJ, Boyer DS, Slakter
JS, Francois CG.Complement C3 inhibitor pegcetacoplan for geographic atrophy secondary to agerelated macular degeneration: a randomized phase 2
trial. Ophthalmology. 2020;127(2):186–95. https://
doi.org/10.1016/j.ophtha.2019.07.011. Epub 2019
Jul 16.
46. Jaffe GJ, Westby K, Csaky KG, Monés J, Pearlman
JA, Patel SS, Joondeph BC, Randolph J, Masonson
H, Rezaei KA. C5 inhibitor avacincaptad pegol
for geographic atrophy due to age-related macular
degeneration: a randomized pivotal phase 2/3 trial.
Ophthalmology. 2021;128(4):576–86. https://doi.
org/10.1016/j.ophtha.2020.08.027. Epub 2020 Sep
1.
47. Wykoff CC, Rosenfeld PJ, Waheed NK, Singh
RP, Ronca N, Slakter JS, Staurenghi G, Monés
J, Baumal CR, Saroj N, Metlapally R, Ribeiro
R. Characterizing new-onset exudation in the
randomized phase 2 FILLY trial of complement
inhibitor pegcetacoplan for geographic atrophy.
Ophthalmology. 2021;128(9):1325–36. https://doi.
org/10.1016/j.ophtha.2021.02.025. Epub 2021 Mar
10.
48. Yehoshua Z, de Amorim Garcia Filho CA, Nunes
RP, Gregori G, Penha FM, Moshfeghi AA, Zhang
392
https://t.me/medicina_free
13 Macular Degeneration, Geographic Atrophy, andInherited Retinal Disorders
K, Sadda S, Feuer W, Rosenfeld PJ. Systemic
complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study. Ophthalmology.
2014;121(3):693–701. https://doi.org/10.1016/j.
ophtha.2013.09.044. Epub 2013 Nov 26.
49. Halawa OA, Lin JB, Miller JW, Vavvas DG. A
review of completed and ongoing complement
inhibitor trials for geographic atrophy secondary to age-related macular degeneration. J Clin
Med. 2021;10(12):2580. https://doi.org/10.3390/
jcm10122580.
50. Riedl S, Vogl WD, Mai J, Reiter GS, Lachinov D,
Grechenig C, McKeown A, Scheibler L, Bogunović
H, Schmidt-Erfurth U.The effect of pegcetacoplan
treatment on photoreceptor maintenance in geographic atrophy monitored by articial intelligencebased OCT analysis. Ophthalmol Retina.
2022;6(11):1009–18. https://doi.org/10.1016/j.
oret.2022.05.030. Epub 2022 Jun 3.
51. Li L, Yu Y, Lin S, Hu J. Changes in best-corrected
visual acuity in patients with dry age-related macular degeneration after stem cell transplantation:
systematic review and meta-analysis. Stem Cell
Res Ther. 2022;13(1):237. https://doi.org/10.1186/
s13287- 022- 02931- y.
52. Van Gelder RN, Chiang MF, Dyer MA,
Greenwell TN, Levin LA, Wong RO, Svendsen
CN. Regenerative and restorative medicine for
eye disease. Nat Med. 2022;28(6):1149–56.
https://doi.org/10.1038/s41591- 022- 01862- 8.
Epub 2022 Jun 17. Erratum in: Nat Med.
2022;28(10):2218.
53. Kashani AH, Lebkowski JS, Rahhal FM, Avery RL,
Salehi-Had H, Chen S, Chan C, Palejwala N, Ingram
A, Dang W, Lin CM, Mitra D, Pennington BO,
Hinman C, Faynus MA, Bailey JK, Mohan S, Rao
N, Johnson LV, Clegg DO, Hinton DR, Humayun
MS.One-year follow-up in a phase 1/2a clinical trial
of an allogeneic RPE cell bioengineered implant
for advanced dry age-related macular degeneration.
Transl Vis Sci Technol. 2021;10(10):13. https://doi.
org/10.1167/tvst.10.10.13.
54. Duke-Elder S, Dobree JH. Diseases of the retina. In:
Duke-Elder, Ed., System of Ophthalmology. Henry
Kimpton, London. 1967;10:126–7.
55. Dryja TP, McGee TL, Reichel E, Hahn LB, Cowley
GS, Yandell DW, Sandberg MA, Berson EL.A point
mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature. 1990;343(6256):364–6.
https://doi.org/10.1038/343364a0.
56. Branham K, Schlegel D, Fahim AT, Jayasundera
KT.Genetic testing for inherited retinal degenerations: triumphs and tribulations. Am J Med
Genet C Semin Med Genet. 2020;184(3):571–7.
https://doi.org/10.1002/ajmg.c.31835. Epub 2020
Aug 31.
57. Goetz KE, Reeves MJ, Gagadam S, Blain D,
Bender C, Lwin C, Naik A, Tumminia SJ, Hufnagel
RB. Genetic testing for inherited eye conditions
in over 6,000 individuals through the eyeGENE
network. Am J Med Genet C Semin Med Genet.
2020;184(3):828–37. https://doi.org/10.1002/
ajmg.c.31843. Epub 2020 Sep 7.
58. Taylor RL, Parry NRA, Barton SJ, Campbell C,
Delaney CM, Ellingford JM, Hall G, Hardcastle
C, Morarji J, Nichol EJ, Williams LC, Douzgou S,
Clayton-Smith J, Ramsden SC, Sharma V, Biswas
S, Lloyd IC, Ashworth JL, Black GC, Sergouniotis
PI. Panel-based clinical genetic testing in 85 children with inherited retinal disease. Ophthalmology.
2017;124(7):985–91. https://doi.org/10.1016/j.oph-
tha.2017.02.005. Epub 2017 Mar 22.
59. Ellingford JM, Sergouniotis PI, Lennon R,
Bhaskar S, Williams SG, Hillman KA, O’Sullivan
J, Hall G, Ramsden SC, Lloyd IC, Woolf AS,
Black GC. Pinpointing clinical diagnosis through
whole exome sequencing to direct patient care:
a case of Senior-Loken syndrome. Lancet.
2015;385(9980):1916. https://doi.org/10.1016/
S0140- 6736(15)60496- 2.
60. Stone EM, Andorf JL, Whitmore SS, DeLuca AP,
Giacalone JC, Streb LM, Braun TA, Mullins RF,
Scheetz TE, Shefeld VC, Tucker BA. Clinically
focused molecular investigation of 1000 consecutive families with inherited retinal disease.
Ophthalmology. 2017;124(9):1314–31. https://doi.
org/10.1016/j.ophtha.2017.04.008. Epub 2017 May
27.
61. Robson AG, Frishman LJ, Grigg J, Hamilton R,
Jeffrey BG, Kondo M, Li S, McCulloch DL.ISCEV
standard for full-eld clinical electroretinography
(2022 update). Doc Ophthalmol. 2022;144(3):165–
77. https://doi.org/10.1007/s10633- 022- 09872- 0.
Epub 2022 May 5.
62. Yung M, Klufas MA, Sarraf D.Clinical applications
of fundus autouorescence in retinal disease. Int J
Retina Vitreous. 2016;2:12. https://doi.org/10.1186/
s40942- 016- 0035- x.
63. Ogura S, Yasukawa T, Kato A, Usui H, Hirano Y,
Yoshida M, Ogura Y. Wide-eld fundus autouorescence imaging to evaluate retinal function in
patients with retinitis pigmentosa. Am J Ophthalmol.
2014;158(5):1093–8. https://doi.org/10.1016/j.
ajo.2014.07.021. Epub 2014 Jul 22.
64. Tan CS, Ngo WK, Cheong KX.Comparison of choroidal thicknesses using swept source and spectral
domain optical coherence tomography in diseased
and normal eyes. Br J Ophthalmol. 2015;99(3):354–
8. https://doi.org/10.1136/bjophthalmol- -
2014- 305331. Epub 2014 Oct 1.
65. Tan CS, Sadda SR.Swept source optical coherence
tomography. In: Meyer CH, Saxena S, Sadda SVR,
editors. Spectral domain optical coherence tomography in macular diseases. New Delhi: Springer; 2017.
p.59–77.
66. Triolo G, Pierro L, Parodi MB, De Benedetto
U, Gagliardi M, Manitto MP, Bandello
F. Spectral-domain optical coherence tomography ndings in patients with retinitis pigmentosa.
References
https://t.me/medicina_free
393
Ophthalmic Res. 2013;50(3):160–4. https://doi.
org/10.1159/000351681. Epub 2013 Aug 28.
67. Liu G, Liu X, Li H, Du Q, Wang F.Optical coherence
tomographic analysis of retina in retinitis pigmentosa patients. Ophthalmic Res. 2016;56(3):111–22.
https://doi.org/10.1159/000445063. Epub 2016 Jun
29.
68. Michaelides M, Hunt DM, Moore AT. The genetics of inherited macular dystrophies. J Med Genet.
2003;40(9):641–50. https://doi.org/10.1136/
jmg.40.9.641.
69. Heath Jeffery RC, Mukhtar SA, McAllister IL,
Morgan WH, Mackey DA, Chen FK.Inherited retinal diseases are the most common cause of blindness in the working-age population in Australia.
Ophthalmic Genet. 2021;42(4):431–9. https://doi.
org/10.1080/13816810.2021.1913610. Epub 2021
May 3. Erratum in: Ophthalmic Genet. 2021:1.
70. Hamel C. Retinitis pigmentosa. Orphanet
J Rare Dis. 2006;1:40. https://doi.
org/10.1186/1750- 1172- 1- 40.
71. Hartong DT, Berson EL, Dryja TP.Retinitis pigmentosa. Lancet. 2006;368(9549):1795–809. https://doi.
org/10.1016/S0140- 6736(06)69740- 7.
72. Chassine T, Bocquet B, Daien V, Avila-Fernandez A,
Ayuso C, Collin RW, Corton M, Hejtmancik JF, van
den Born LI, Klevering BJ, Riazuddin SA, Sendon
N, Lacroux A, Meunier I, Hamel CP. Autosomal
recessive retinitis pigmentosa with RP1 mutations is associated with myopia. Br J Ophthalmol.
2015;99(10):1360–5. https://doi.org/10.1136/
bjophthalmol- 2014- 306224. Epub 2015 Apr 16.
73. Kumaran N, Moore AT, Weleber RG, Michaelides
M. Leber congenital amaurosis/early-onset severe
retinal dystrophy: clinical features, molecular genetics and therapeutic interventions. Br J Ophthalmol.
2017;101(9):1147–54. https://doi.org/10.1136/
bjophthalmol- 2016- 309975. Epub 2017 Jul 8.
Erratum in: Br J Ophthalmol. 2019;103(6):862.
74. Kitiratschky VB, Wilke R, Renner AB, Kellner U,
Vadalà M, Birch DG, Wissinger B, Zrenner E, Kohl
S. Mutation analysis identies GUCY2D as the
major gene responsible for autosomal dominant progressive cone degeneration. Invest Ophthalmol Vis
Sci. 2008;49(11):5015–23. https://doi.org/10.1167/
iovs.08- 1901. Epub 2008 May 16.
75. Pasadhika S, Fishman GA, Stone EM, Lindeman
M, Zelkha R, Lopez I, Koenekoop RK, Shahidi
M.Differential macular morphology in patients with
RPE65-, CEP290-, GUCY2D-, and AIPL1-related
Leber congenital amaurosis. Invest Ophthalmol Vis
Sci. 2010;51(5):2608–14. https://doi.org/10.1167/
iovs.09- 3734. Epub 2009 Dec 3.
76. Maguire AM, Bennett J, Aleman EM, Leroy
BP, Aleman TS. Clinical perspective: treating
RPE65-associated retinal dystrophy. Mol Ther.
2021;29(2):442–63. https://doi.org/10.1016/j.
ymthe.2020.11.029. Epub 2020 Dec 3.
77. Talib M, van Schooneveld MJ, van Duuren RJG, Van
Cauwenbergh C, Ten Brink JB, De Baere E, Florijn
RJ, Schalij-Delfos NE, Leroy BP, Bergen AA, Boon
CJF. Long-term follow-up of retinal degenerations
associated with LRAT mutations and their comparability to phenotypes associated with RPE65 mutations. Transl Vis Sci Technol. 2019;8(4):24. https://
doi.org/10.1167/tvst.8.4.24.
78. Leroy BP, Birch DG, Duncan JL, Lam BL, Koenekoop
RK, Porto FBO, Russell SR, Girach A.Leber congenital amaurosis due to CEP290 mutations- severe
vision impairment with a high unmet medical need:
a review. Retina. 2021;41(5):898–907. https://doi.
org/10.1097/IAE.0000000000003133.
79. May-Simera H, Nagel-Wolfrum K, Wolfrum
U.Cilia—the sensory antennae in the eye. Prog Retin
Eye Res. 2017;60:144–80. https://doi.org/10.1016/j.
preteyeres.2017.05.001. Epub 2017 May 11.
80. Estrada-Cuzcano A, Roepman R, Cremers FP, den
Hollander AI, Mans DA.Non-syndromic retinal ciliopathies: translating gene discovery into therapy.
Hum Mol Genet. 2012;21(R1):R111–24. https://doi.
org/10.1093/hmg/dds298. Epub 2012 Jul 26.
81. Werdich XQ, Place EM, Pierce EA. Systemic diseases associated with retinal dystrophies. Semin
Ophthalmol. 2014;29(5–6):319–28. https://doi.org/
10.3109/08820538.2014.959202.
82. Beales PL, Elcioglu N, Woolf AS, Parker D, Flinter
FA.New criteria for improved diagnosis of BardetBiedl syndrome: results of a population survey. J
Med Genet. 1999;36(6):437–46.
83. Marshall JD, Bronson RT, Collin GB, Nordstrom
AD, Maffei P, Paisey RB, Carey C, Macdermott
S, Russell-Eggitt I, Shea SE, Davis J, Beck S,
Shatirishvili G, Mihai CM, Hoeltzenbein M,
Pozzan GB, Hopkinson I, Sicolo N, Naggert JK,
Nishina PM. New Alström syndrome phenotypes
based on the evaluation of 182 cases. Arch Intern
Med. 2005;165(6):675–83. https://doi.org/10.1001/
archinte.165.6.675.
84. Russell-Eggitt IM, Clayton PT, Coffey R, Kriss A,
Taylor DS, Taylor JF. Alström syndrome. Report
of 22 cases and literature review. Ophthalmology.
1998;105(7):1274–80. https://doi.org/10.1016/
S0161- 6420(98)97033- 6.
85. Romano S, Maffei P, Bettini V, Milan G, Favaretto
F, Gardiman M, Marshall JD, Greggio NA, Pozzan
GB, Collin GB, Naggert JK, Bronson R, Vettor
R. Alström syndrome is associated with short
stature and reduced GH reserve. Clin Endocrinol
(Oxf). 2013;79(4):529–36. https://doi.org/10.1111/
cen.12180. Epub 2013 Mar 26.
86. Dassie F, Favaretto F, Bettini S, Parolin M, Valenti
M, Reschke F, Danne T, Vettor R, Milan G, Maffei
P.Alström syndrome: an ultra-rare monogenic disorder as a model for insulin resistance, type 2 diabetes
mellitus and obesity. Endocrine. 2021;71(3):618–25.
https://doi.org/10.1007/s12020- 021- 02643- y. Epub
2021 Feb 10.
87. Bettini V, Maffei P, Pagano C, Romano S, Milan
G, Favaretto F, Marshall JD, Paisey R, Scolari
F, Greggio NA, Tosetto I, Naggert JK, Sicolo N,
394
https://t.me/medicina_free
13 Macular Degeneration, Geographic Atrophy, andInherited Retinal Disorders
Vettor R. The progression from obesity to type 2
diabetes in Alström syndrome. Pediatr Diabetes.
2012;13(1):59–67. https://doi.org/10.1111/j.1399- -
5448.2011.00789.x. Epub 2011 Jul 3.
88. Baig S, Paisey R, Dawson C, Barrett T, Maffei P,
Hodson J, Rambhatla SB, Chauhan P, Bolton S,
Dassie F, Francomano C, Marshall RP, Belal M,
Skordilis K, Hayer M, Price AM, Cramb R, Edwards
N, Steeds RP, Geberhiwot T.Dening renal phenotype in Alström syndrome. Nephrol Dial Transplant.
2020;35(6):994–1001. https://doi.org/10.1093/ndt/
gfy293.
89. Aliferis K, Hellé S, Gyapay G, Duchatelet S,
Stoetzel C, Mandel JL, Dollfus H. Differentiating
Alström from Bardet-Biedl syndrome (BBS) using
systematic ciliopathy genes sequencing. Ophthalmic
Genet. 2012;33(1):18–22. https://doi.org/10.3109/1
3816810.2011.620055. Epub 2011 Oct 17.
90. Guimaraes TAC, Arram E, Shakarchi AF, Georgiou
M, Michaelides M. Inherited causes of combined
vision and hearing loss: clinical features and molecular genetics. Br J Ophthalmol. 2022;107:1403.
https://doi.org/10.1136/bjo- 2022- 321790. Epub
ahead of print.
91. Ben-Avi R, Rivera A, Hendler K, Sharon D, Banin
E, Khateb S, Yahalom C. Prevalence and associated factors of cystoid macular edema in children
with early onset inherited retinal dystrophies.
Eur J Ophthalmol. 2022;33(2):1109. https://doi.
org/10.1177/11206721221136318. Epub ahead of
print.
92. Fanconi G, Hanhart E, von Albertini A, Uhlinger
E, Dolivo G, Prader A. Die familiäre juvenile
Nephronophthise (die idiopathische parenchymatöse
Schrumpfniere) [Familial, juvenile nephronophthisis (idiopathic parenchymal contracted kidney)].
Helv Paediatr Acta. 1951;6(1):1–49. Undetermined
Language.
93. Senior B, Friedmann AI, Braudo JL. Juvenile
familial nephropathy with tapetoretinal degeneration. A new oculorenal dystrophy. Am J
Ophthalmol. 1961;52:625–33. https://doi.
org/10.1016/0002- 9394(61)90147- 7.
94. Loken AC, Hanssen O, Halvorsen S, Jolster
NJ. Hereditary renal dysplasia and blindness. Acta
Paediatr (Stockh). 1961;50:177–84. https://doi.
org/10.1111/j.1651- 2227.1961.tb08037.x.
95. Ronquillo CC, Bernstein PS, Baehr W. SeniorLøken syndrome: a syndromic form of retinal
dystrophy associated with nephronophthisis. Vis
Res. 2012;75:88–97. https://doi.org/10.1016/j.
visres.2012.07.003. Epub 2012 Jul 20.
96. Joubert M, Eisenring JJ, Robb JP, Andermann
F. Familial agenesis of the cerebellar vermis. A
syndrome of episodic hyperpnea, abnormal eye
movements, ataxia, and retardation. Neurology.
1969;19(9):813–25. https://doi.org/10.1212/
wnl.19.9.813.
97. Wang SF, Kowal TJ, Ning K, Koo EB, Wu AY,
Mahajan VB, Sun Y.Review of ocular manifestations
of Joubert syndrome. Genes (Basel). 2018;9(12):605.
https://doi.org/10.3390/genes9120605.
98. Zhang J, Wang L, Chen W, Duan J, Meng Y, Yang
H, Guo Q.Whole exome sequencing facilitated the
diagnosis in four Chinese pediatric cases of Joubert
syndrome related disorders. Am J Transl Res.
2022;14(7):5088–97.
99. Hartill V, Szymanska K, Sharif SM, Wheway G,
Johnson CA. Meckel-Gruber syndrome: an update
on diagnosis, clinical management, and research
advances. Front Pediatr. 2017;5:244. https://doi.
org/10.3389/fped.2017.00244.
100. Spiteri Cornish K, Ho J, Downes S, Scott NW,
Bainbridge J, Lois N.The epidemiology of Stargardt
disease in the United Kingdom. Ophthalmol Retina.
2017;1(6):508–13. https://doi.org/10.1016/j.
oret.2017.03.001. Epub 2017 Apr 21.
101. Huang D, Heath Jeffery RC, Aung-Htut MT,
McLenachan S, Fletcher S, Wilton SD, Chen
FK. Stargardt disease and progress in therapeutic
strategies. Ophthalmic Genet. 2022;43(1):1–26.
https://doi.org/10.1080/13816810.2021.1966053.
Epub 2021 Aug 29.
102. Strauss RW, Muñoz B, Ho A, Jha A, Michaelides M,
Mohand-Said S, Cideciyan AV, Birch D, Hariri AH,
Nittala MG, Sadda S, Scholl HPN, ProgStar Study
Group. Incidence of atrophic lesions in Stargardt
disease in the progression of atrophy secondary to
Stargardt disease (ProgStar) study: report no. 5.
JAMA Ophthalmol. 2017;135(7):687–95. https://
doi.org/10.1001/jamaophthalmol.2017.1121.
103. Klufas MA, Tsui I, Sadda SR, Hosseini H,
Schwartz SD. Ultrawidefield autofluoresence in ABCA4 Stargardt disease. Retina.
2018;38(2):403–15. https://doi.org/10.1097/
IAE.0000000000001567.
104. Roborel de Climens A, Tugaut B, Dias Barbosa C,
Buggage R, Brun-Strang C. Living with Stargardt
disease: insights from patients and their parents.
Ophthalmic Genet. 2021;42(2):150–60. https://doi.
org/10.1080/13816810.2020.1855663. Epub 2020
Dec 11.
105. Kubota R, Birch DG, Gregory JK, Koester
JM.Randomised study evaluating the pharmacodynamics of emixustat hydrochloride in subjects with
macular atrophy secondary to Stargardt disease.
Br J Ophthalmol. 2022;106(3):403–8. https://doi.
org/10.1136/bjophthalmol- 2020- 317712. Epub 2020
Nov 19.
106. Radu RA, Mata NL, Nusinowitz S, Liu X, Sieving
PA, Travis GH.Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of
recessive Stargardt’s macular degeneration. Proc
Natl Acad Sci U S A. 2003;100(8):4742–7. https://
doi.org/10.1073/pnas.0737855100. Epub 2003 Apr
1.
107. Wang Y, Ma X, Muthuraman P, Raja A, Jayaraman
A, Petrukhin K, Ciof CL, Ma JX, Moiseyev G.The
novel visual cycle inhibitor (±)-RPE65-61 protects
retinal photoreceptors from light-induced degenera-
References
https://t.me/medicina_free
395
tion. PLoS One. 2022;17(10):e0269437. https://doi.
org/10.1371/journal.pone.0269437.
108. Mehat MS, Sundaram V, Ripamonti C, Robson
AG, Smith AJ, Borooah S, Robinson M, Rosenthal
AN, Innes W, Weleber RG, Lee RWJ, Crossland
M, Rubin GS, Dhillon B, Steel DHW, Anglade E,
Lanza RP, Ali RR, Michaelides M, Bainbridge
JWB.Transplantation of human embryonic stem cellderived retinal pigment epithelial cells in macular
degeneration. Ophthalmology. 2018;125(11):1765–
75. https://doi.org/10.1016/j.ophtha.2018.04.037.
Epub 2018 Jun 5.
109. Gullapalli VK, Zarbin MA.New prospects for retinal pigment epithelium transplantation. Asia Pac J
Ophthalmol (Phila). 2022;11(4):302–13. https://doi.
org/10.1097/APO.0000000000000521. Epub 2022
Aug 30.
110. Johnson AA, Guziewicz KE, Lee CJ, Kalathur
RC, Pulido JS, Marmorstein LY, Marmorstein
AD. Bestrophin 1 and retinal disease. Prog Retin
Eye Res. 2017;58:45–69. https://doi.org/10.1016/j.
preteyeres.2017.01.006. Epub 2017 Jan 30.
111. Vedantham V, Ramasamy K. Optical coherence
tomography in Best’s disease: an observational
case report. Am J Ophthalmol. 2005;139(2):351–3.
https://doi.org/10.1016/j.ajo.2004.07.039.
112. O’Gorman S, Flaherty WA, Fishman GA, Berson
EL. Histopathologic ndings in Best’s vitelliform macular dystrophy. Arch Ophthalmol.
1988;106(9):1261–8. https://doi.org/10.1001/archo
pht.1988.01060140421045.
113. Battaglia Parodi M, Iacono P, Romano F, Bandello
F. Spectral domain optical coherence tomography
features in different stages of best vitelliform macular dystrophy. Retina. 2018;38(5):1041–6. https://
doi.org/10.1097/IAE.0000000000001634.
114. Qian CX, Charran D, Strong CR, Steffens TJ,
Jayasundera T, Heckenlively JR.Optical coherence
tomography examination of the retinal pigment
epithelium in best vitelliform macular dystrophy.
Ophthalmology. 2017;124(4):456–63. https://doi.
org/10.1016/j.ophtha.2016.11.022. Epub 2017 Feb
7.
115. Burgess R, Millar ID, Leroy BP, Urquhart JE,
Fearon IM, De Baere E, Brown PD, Robson AG,
Wright GA, Kestelyn P, Holder GE, Webster AR,
Manson FD, Black GC.Biallelic mutation of BEST1
causes a distinct retinopathy in humans. Am J Hum
Genet. 2008;82(1):19–31. https://doi.org/10.1016/j.
ajhg.2007.08.004.
116. Tsunoda K, Hanazono G.Microstructural changes
of photoreceptor layers detected by ultrahighresolution SD-OCT in patients with autosomal
recessive bestrophinopathy. Am J Ophthalmol Case
Rep. 2022;28:101706. https://doi.org/10.1016/j.
ajoc.2022.101706.
117. Brecher R, Bird AC.Adult vitelliform macular dystrophy. Eye (Lond). 1990;4(Pt 1):210–5. https://doi.
org/10.1038/eye.1990.28.
118. Querques G, Forte R, Querques L, Massamba N,
Souied EH.Natural course of adult-onset foveomacular vitelliform dystrophy: a spectral-domain optical
coherence tomography analysis. Am J Ophthalmol.
2011;152(2):304–13. https://doi.org/10.1016/j.
ajo.2011.01.047. Epub 2011 Jun 12.
119. Gass JD. A clinicopathologic study of a peculiar
foveomacular dystrophy. Trans Am Ophthalmol
Soc. 1974;72:139–56.
120. Patrinely JR, Lewis RA, Font RL. Foveomacular
vitelliform dystrophy, adult type. A clinicopathologic study including electron microscopic observations. Ophthalmology. 1985;92(12):1712–8. https://
doi.org/10.1016/s0161- 6420(85)34097- 6.
121. Bansal R, Yangzes S, Singh R, Katoch D, Dogra MR,
Gupta V, Gupta A.Retinal pigment epithelium aperture: a late-onset complication in adult-onset foveomacular vitelliform dystrophy. Indian J Ophthalmol.
2018;66(1):83–8. https://doi.org/10.4103/ijo.
IJO_676_17.
122. Birtel J, von Landenberg C, Gliem M, Gliem C,
Reimann J, Kunz WS, Herrmann P, Betz C, Caswell
R, Nesbitt V, Kornblum C, Charbel IP.Mitochondrial
retinopathy. Ophthalmol Retina. 2022;6(1):65–79.
https://doi.org/10.1016/j.oret.2021.02.017. Epub
2021 Jul 10.
123. Musta D, Bharathan SP, Calderon R, Nagiel
A.Human cellular models for retinal disease: from
induced pluripotent stem cells to organoids. Retina.
2022;42(10):1829–35. https://doi.org/10.1097/
IAE.0000000000003571.
124. Burnight ER, Gupta M, Wiley LA, Annson KR,
Tran A, Triboulet R, Hoffmann JM, Klaahsen
DL, Andorf JL, Jiao C, Sohn EH, Adur MK, Ross
JW, Mullins RF, Daley GQ, Schlaeger TM, Stone
EM, Tucker BA. Using CRISPR-Cas9 to generate gene-corrected autologous iPSCs for the treatment of inherited retinal degeneration. Mol Ther.
2017;25(9):1999–2013. https://doi.org/10.1016/j.
ymthe.2017.05.015. Epub 2017 Jun 12.
125. Garafalo AV, Cideciyan AV, Héon E, Sheplock R,
Pearson A, WeiYang YC, Sumaroka A, Aguirre GD,
Jacobson SG. Progress in treating inherited retinal
diseases: early subretinal gene therapy clinical trials and candidates for future initiatives. Prog Retin
Eye Res. 2020;77:100827. https://doi.org/10.1016/j.
preteyeres.2019.100827. Epub 2019 Dec 30.
126. Maguire AM, Russell S, Wellman JA, Chung DC, Yu
ZF, Tillman A, Wittes J, Pappas J, Elci O, Marshall
KA, McCague S, Reichert H, Davis M, Simonelli F,
Leroy BP, Wright JF, High KA, Bennett J.Efcacy,
safety, and durability of voretigene neparvovecrzyl in RPE65 mutation-associated inherited
retinal dystrophy: results of phase 1 and 3 trials.
Ophthalmology. 2019;126(9):1273–85. https://doi.
org/10.1016/j.ophtha.2019.06.017. Epub 2019 Jun
22.
127. Pennesi ME, Schlecther CL.The evolution of retinal
gene therapy: from clinical trials to clinical prac-
396
https://t.me/medicina_free
13 Macular Degeneration, Geographic Atrophy, andInherited Retinal Disorders
tice. Ophthalmology. 2020;127(2):148–50. https://
doi.org/10.1016/j.ophtha.2019.12.003. Erratum in:
Ophthalmology. 2020;127(4):557.
128. Testa F, Melillo P, Di Iorio V, Iovino C, Farinaro F,
Karali M, Ban S, Rossi S, Della Corte M, Simonelli
F. Visual function and retinal changes after voretigene neparvovec treatment in children with biallelic RPE65-related inherited retinal dystrophy. Sci
Rep. 2022;12(1):17637. https://doi.org/10.1038/
s41598- 022- 22180- 6.
129. Gange WS, Sisk RA, Besirli CG, Lee TC, Havunjian
M, Schwartz H, Borchert M, Sengillo JD, Mendoza
C, Berrocal AM, Nagiel A. Perifoveal chorioretinal
atrophy after subretinal voretigene neparvovec-rzyl
for RPE65-mediated Leber congenital amaurosis.
Ophthalmol Retina. 2022;6(1):58–64. https://doi.
org/10.1016/j.oret.2021.03.016. Epub 2021 Apr 8.
130. Deng C, Zhao PY, Branham K, Schlegel D, Fahim
AT, Jayasundera TK, Khan N, Besirli CG. Realworld outcomes of voretigene neparvovec treatment in pediatric patients with RPE65-associated
Leber congenital amaurosis. Graefes Arch Clin
Exp Ophthalmol. 2022;260(5):1543–50. https://doi.
org/10.1007/s00417- 021- 05508- 2. Epub 2022 Jan
10.
131. Parker MA, Erker LR, Audo I, Choi D, MohandSaid S, Sestakauskas K, Benoit P, Appelqvist T,
Krahmer M, Ségaut-Prévost C, Lujan BJ, Faridi
A, Chegarnov EN, Steinkamp PN, Ku C, da Palma
MM, Barale PO, Ayelo-Scheer S, Lauer A, Stout
T, Wilson DJ, Weleber RG, Pennesi ME, Sahel JA,
Yang P. Three-year safety results of SAR422459
(EIAV-ABCA4) gene therapy in patients with
ABCA4-associated Stargardt disease: an open-label
dose-escalation phase I/IIa clinical trial, cohorts 1-5.
Am J Ophthalmol. 2022;240:285–301. https://doi.
org/10.1016/j.ajo.2022.02.013. Epub 2022 Mar 4.
132. Pennesi ME, Yang P, Birch DG, Weng CY, Moore
AT, Iannaccone A, Comander JI, Jayasundera T,
Chulay J, XLRS-001 Study Group. Intravitreal
delivery of rAAV2tYF-CB-hRS1 vector for gene
augmentation therapy in patients with X-linked retinoschisis: 1-year clinical results. Ophthalmol Retina.
2022;6(12):1130–44. https://doi.org/10.1016/j.
oret.2022.06.013. Epub 2022 Jun 30.
133. Santos A, Humayun MS, de Juan E Jr, Greenburg
RJ, Marsh MJ, Klock IB, Milam AH.Preservation
of the inner retina in retinitis pigmentosa. A
morphometric analysis. Arch Ophthalmol.
1997;115(4):511–5. https://doi.org/10.1001/archo
pht.1997.01100150513011.
134. De Silva SR, Moore AT.Optogenetic approaches to
therapy for inherited retinal degenerations. J Physiol.
2022;600(21):4623–32. https://doi.org/10.1113/
JP282076. Epub 2022 Aug 17.
135. Sahel JA, Boulanger-Scemama E, Pagot C, Arleo
A, Galluppi F, Martel JN, Esposti SD, Delaux A, de
Saint Aubert JB, de Montleau C, Gutman E, Audo
I, Duebel J, Picaud S, Dalkara D, Blouin L, Taiel
M, Roska B. Partial recovery of visual function in
a blind patient after optogenetic therapy. Nat Med.
2021;27(7):1223–9. https://doi.org/10.1038/s41591- -
021- 01351- 4. Epub 2021 May 24.
136. Fujinami K, Yang L, Joo K, Tsunoda K, Kameya
S, Hanazono G, Fujinami-Yokokawa Y, Arno G,
Kondo M, Nakamura N, Kurihara T, Tsubota K,
Zou X, Li H, Park KH, Iwata T, Miyake Y, Woo SJ,
Sui R, East Asia Inherited Retinal Disease Society
Study Group. Clinical and genetic characteristics of
east Asian patients with occult macular dystrophy
(Miyake disease): east Asia occult macular dystrophy studies report number 1. Ophthalmology.
2019;126(10):1432–44. https://doi.org/10.1016/j.
ophtha.2019.04.032. Epub 2019 Apr 25.
137. Yahya S, Smith CEL, Poulter JA, McKibbin M,
Arno G, Ellingford J, Kämpjärvi K, Khan MI,
Cremers FPM, Hardcastle AJ, Castle B, Steel
DHW, Webster AR, Black GC, El-Asrag ME,
Ali M, Toomes C, Inglehearn CF, UK Inherited
Retinal Dystrophy Consortium, Genomics England
Research Consortium. Late-onset autosomal dominant macular degeneration caused by deletion of the
CRX gene. Ophthalmology. 2023;130(1):68–76.
https://doi.org/10.1016/j.ophtha.2022.07.023. Epub
2022 Aug 5.
138. Sohocki MM, Sullivan LS, Mintz-Hittner HA, Birch
D, Heckenlively JR, Freund CL, McInnes RR, Daiger
SP. A range of clinical phenotypes associated with
mutations in CRX, a photoreceptor transcriptionfactor gene. Am J Hum Genet. 1998;63(5):1307–15.
https://doi.org/10.1086/302101.
139. Spaide RF. Treatment of Sorsby fundus dystrophy with anti-tumor necrosis factor-alpha medication. Eye (Lond). 2022;36(9):1810–2. https://doi.
org/10.1038/s41433- 021- 01735- 3. Epub 2021 Aug
10.
140. Bryan JM, Rojas CN, Mirza RG.Macular ndings
expedite accurate diagnosis of MIDD in a young
female patient with newly diagnosed diabetes. Am J
Ophthalmol Case Rep. 2022;27:101578. https://doi.
org/10.1016/j.ajoc.2022.101578.
141. Ambonville C, Meas T, Lecleire-Collet A, LaloiMichelin M, Virally M, Kevorkian JP, Paques M,
Massin P, Guillausseau PJ. Macular pattern dystrophy in MIDD: long-term follow-up. Diabetes Metab.
2008;34(4 Pt 1):389–91. https://doi.org/10.1016/j.
diabet.2008.05.002. Epub 2008 Jun 30.
142. Agarwal A, editor. Gass’ atlas of macular diseases,
vol. 1. 5th ed. Saunders/Elsevier; 2012. p.240–436.
Vascular Malformations,
https://t.me/medicina_free
Childhood Cancer Predisposition
Syndromes andTheir Systemic
Associations
14
14.1 Introduction
Retinal vascular malformations and tumours
arising in the various structures of the eye are
rare and benign in their course. However, they
compromise the vision of the affected eye to
varying degrees. More importantly, however,
these have strong genetic implications and systemic associations. Complications and morbidity arising from these can be anticipated by
ophthalmic examination long before these manifest clinically. Retinoblastoma (RB), retinal
capillary hemangioblastoma, retinal astrocytoma, Neurobromatosis type1 and type 2, and
Ciliary body medulloepithelioma are some of
the childhood cancer predisposition syndromes
that have signicant ocular manifestations.
Neurobromatosis type 1 is associated with
optic pathway glioma. These patients may
develop high-grade glioma in the brain and
malignant peripheral nerve sheath tumours.
Detection of highly characteristic retinal astrocytomas associated with tuberous sclerosis can
help to timely detect subependymal giant cell
astrocytoma. Retinoblastoma, arising from the
primitive retina, is one of the most common
intraocular malignant tumours in infancy and
early childhood. It is locally invasive if not
detected in time, leading to distant metastasis
and fatal outcomes. External beam radiation
therapy and chemotherapy for retinoblastoma
are associated with the late development of
osteogenic sarcomas and other cancers. The
most common intraocular malignant tumour in
adulthood is malignant uveal melanoma, which
may have distant metastasis before it gets
detected. Discussion on this cancer is beyond the
scope of this chapter and is not discussed hereafter. The following retinal vascular malformations and retinal astrocytoma have strong
systemic associations and will be discussed in
some detail.
1. Retinal capillary hemangioblastoma (von
Hippel-Lindau’s disease).
2. Capillary hemangioma of the choroid (Sturge-
Weber syndrome).
3. Arteriovenous malformation (Wyburn Mason
syndrome).
4. Congenital retinal macrovessels.
5. Cavernous hemangioma of the retina.
6. Retinal astrocytoma.
7. Neurobromatosis type 1.
8. Neurobromatosis type 2.
9. Retinoblastoma.
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
A. Gupta et al., Ophthalmic Signs in Practice of Medicine,
https://doi.org/10.1007/978-981-99-7923-3_14
397
14 Vascular Malformations, Childhood Cancer Predisposition Syndromes andTheir Systemic Associations
https://t.me/medicina_free
398
14.2 Retinal Capillary
Hemangioblastoma
14.2.1 Retinal Capillary
Hemangioblastoma—
Historical Aspects
Retinal capillary hemangioblastoma, more popularly called retinal angioma, is not rare, with a
point prevalence of heterozygotes in 1:54,000
and an estimated rate of 1:36,000 in live births
[1]. It is a multisystem disorder, but patients in
their mid-twenties usually present to their ophthalmologist with visual complaints. In large tertiary care centres, these patients may receive
ocular screening from other disciplines. First
described by von Hippel in 1904 as a rare retinal
angioma, its association with a cerebellar hemangioblastoma was rst described as Lindau’s disease in 1927, and only about a decade later, it got
the name von Hippel Lindau’s (VHL) disease, a
name that has stuck. https://eyewiki.org/w/index.
php?title=Retinal_Capillary_
Hemangioblastoma_and_von_Hippel-Lindau_
Disease&oldid=81219
genes (antioncogenes) [3]. People born with a
single copy of the abnormal gene and develop,
post-conception, a somatic mutation at random
(by loss, mutation, or methylation) in the wildtype allele in a single cell develop a sporadic
single organ disease not transmittable to the offspring [4, 5]. Typically, the VHL protein is
responsible for the degradation of Hypoxiainducible factor under normoxic conditions. The
mutant VHL protein cannot carry out this degradation and hence cannot control the transcription
of the VEGF and PDGF mRNA, leading to the
formation of hemangioblastoma [6]. The other
cancers caused by tumour suppressor genes are
seen in sporadic and inherited forms; the prime
examples, among several others, are retinoblastoma, neuroblastoma, and the Wilms’ tumour [3].
Patients born with complete deletion were less
likely to develop retinal lesions than those born
with partial deletion, missense, or nonsense
mutations [7].
14.2.3 Retinal Capillary
Hemangioblastoma—
Systemic Associations
14.2.2 Retinal Capillary
Hemangioblastoma—Genetic
Aspects
Germline mutations in a tumour suppressor gene
located on the short arm of chromosome 3in the
region 3p25-26 cause VHL disease [2]. In most
patients, the VHL disease is autosomal dominant
with a high degree of penetrance, but in about
20%, it is seen as a sporadic tumour. The tumour
suppressor genes typically control and regulate
the unbridled proliferation of cells, and the inactivation of both gene copies leads to cancer formation. It is a prime example of Knudson’s
two-hit theory regarding the tumour suppressor
The inherited VHL disease develops multiple
tumours and cysts in several organs at varying
intervals. The most common among the affected
organs are the kidneys, cerebellum, spinal cord,
pancreas, adrenal glands (pheochromocytoma),
and epididymis in males and broad ligament in
females (Fig.14.1) [8]. Before the institution of
screening programs, mortality before the age of
50 years was common, mainly from cerebellar
hemangioblastoma and clear cell RCC [9, 10].
The RCC develops in up to 70% of patients
with VHL disease [9]. Patients who develop RCC
(44±10.9years) are much older than those who
develop cerebellar hemangioblastoma
(29 ± 10 years) or retinal hemangioblastoma
cd
ab
14.2 Retinal Capillary Hemangioblastoma
https://t.me/medicina_free
399
Fig. 14.1 Dilated, tortuous vessels in the right eye of a
patient with VHL disease (a), especially of the superotemporal quadrant (black arrows), being the feeder vessels
(blue arrow) of the retinal capillary haemangioma (yellow
arrows) in the superotemporal periphery (b). The inferotemporal periphery also shows a retinal angioma (yellow
arrow) (c). Axial CECT abdomen shows multiple cysts of
(25.4±12.7 years), with median survival being
49years [4, 5]. Clustering of clinical features of
VHL in different affected families may occur due
to different mutations in the complex VHL locus
on chromosome 3p25-26 [11]. More than 50% of
inherited VHL may show only one systemic feature [4, 5]. The clinical diagnosis of VHL can be
varying sizes in the pancreas (red arrows) along with a
simple cyst in visualized left kidney (blue arrow).
Interpretation of image (d) by Dr. Chirag Ahuja,
Department of Radiodiagnosis and imaging, Post
Graduate Institute of Medical Education and Research,
Chandigarh, India
made in patients with a positive family history in
the presence of even a single hemangioblastoma
in the retina, nervous system, pheochromocytoma, RCC, or multiple pancreatic cysts
(Fig.14.1). Renal and epididymal cysts are too
common to qualify for a diagnosis of VHL on
their own [9, 10]. (See Box 14.1).
14 Vascular Malformations, Childhood Cancer Predisposition Syndromes andTheir Systemic Associations
https://t.me/medicina_free
400
up to 45% of patients with VHL.Renal cysts are
Box 14.1 Familial Phenotypes in von
Hippel-Lindau Disease
Type Ocular component Systemic associations
Type 1Retinal
hemangioblastoma
Type 2ARetinal
hemangioblastoma
Type 2BRetinal
hemangioblastoma
Type 2CNone Pheochromocytoma
Reduced risk of
pheochromocytoma
CNS
hemangioblastoma;
Pancreatic cysts and
neoplasm;
ccRCC
Pheochromocytoma
CNS
hemangioblastoma
No ccRCC
Pheochromocytoma;
CNS
hemangioblastoma
ccRCC
alone
Abbreviations: CNS central nervous
system; cc clear cell; RCC renal cell
carcinoma.
Adapted with permission of the publishers from Lonser etal. [10].
The nervous system hemangioblastoma is a
thin-walled, encapsulated benign tumour that is
most common in the spinal cord and cerebellum
and least common in the brain stem. These have
variable periods of growth alternating with periods of growth arrest. These become symptomatic
depending upon the availability of space to
expand, most of the expansion occurring in the
cysts rather than the solid tumours. Thus, the spinal cord and brain stem hemangioblastoma
present earlier than the cerebellar tumours/cysts.
often bilateral and multiple and remain asymptomatic. Detection of these cysts and tumours,
before they become symptomatic in a screening
program, improves the outcome of these tumours
(Box 14.2).
Box 14.2 Screening Guidelines for von
Hippel-Lindau Disease
Beginning age in years for the tests
Exam/Test/Labs <5 5 11 15 30 65 and >
History and
physical exam
BP and pulse Annual from the age of 2years
Dilated fundus
exam
Blood
metanephrine
24-hour urine
catecholamines
MRI brain and
spine
MRI abdomen Every 2
Audiogram Every 2 years from
MRI internal
auditory canal
Annual from the age of 1year
From <1 till 30years
every 6–12months
Annual from 5 to
65years of age
Every 2 years from
11 to 65years of
age
years from
15 to
65years of
age
11 to 65years of
age
Once
Adapted with permission from: https://
www.vhl.org/patients/clinical-care/
screening/.
Detected well in time, surgery can safely excise
these [12]. Because of the pleomorphic nature of
the VHL disease, a detailed family history,
genetic testing and counselling, and comprehensive screening and care are required by a multi-
14.2.4 Retinal Capillary
Hemangioblastoma
(Angiomas)
disciplinary team [10]. The kidneys have multiple
cysts and solid tumours. Nearly 40% of the partial nephrectomy samples in VHL disease had
clear cell renal carcinoma (RCC). Most solid
lesions and 21% of the renal cysts harboured
RCC [13]. The VHL is the commonest cause of
inherited RCC. It is a major malignant lesion
with variable periods of growth. It may be seen in
Retinal hemangioblastoma (angiomas) is a common lesion in patients with VHL disease and may
occur in 50–60% of the patients. Although the
usual age of presentation is mid-twenties, retinal
screening of their offspring may discover retinal
hemangioblastoma (RH) as early as one year.
This red-coloured RH in the inherited VHL is
Annual after
30 throughout
life
Skip
routine
after
65
Skip
routine
after
65
Skip
routine
after
65
Skip
routine
after
65
Соседние файлы в папке Библиотека им академика М.И. Перельмана