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Pathological findings in enucleated eyes of patients with neurofibromatosis type 1: report of a case with 15-year follow-up and review of 14 patients in the literature

BMC Ophthalmology volume 24, Article number: 341 (2024) Cite this article

Abstract

Backgrounds

Iris nodules are frequently noted as clinical manifestations of neurofibromatosis type 1 but the other intraocular manifestations are rare. The purpose of this study is to present a patient with a phthisic eye who underwent enucleation for a cosmetic reason after 15-year follow-up and also to review 14 patients with enucleation described in the literature.

Case presentation

A 17-year-old man with neurofibromatosis type 1 from infancy underwent the enucleation of phthisic left eye and also had the resection of eyelid subcutaneous mass lesions on the left side for a cosmetic reason. He had undergone four-time preceding surgeries for eyelid and orbital mass reduction on the left side in childhood and had developed total retinal detachment 10 years previously. Pathologically, the enucleated eye showed massive retinal gliosis positive for both S-100 and glial fibrillary acidic protein (GFAP) in the area with involvement of the detached retinal neuronal layer, together with a more fibrotic lesion along the choroid which were, in contrast, negative for both S-100 and GFAP. The choroid, ciliary body, and iris did not show apparent neurofibroma while episcleral neurofibroma was present.

Literature review

In review of enucleated eyes of 14 patients in the literature, buphthalmic eyes with early-onset glaucoma on the unilateral side was clinically diagnosed in 9 patients who frequently showed varying extent of hemifacial neurofibromatosis which involved the eyelid and orbit on the same side. Pathologically, neurofibromas in varying extent were found in the choroid of 12 patients. One patient showed choroidal malignant melanoma on the left side and fusiform enlargement of the optic nerve on the right side suspected of optic nerve glioma. The phthisic eye in another patient showed massive retinal gliosis similar to the present patient.

Conclusions

In summary of the 15 patients with neurofibromatosis type 1, including the present patient, buphthalmic or phthisic eyes with no vision were enucleated for cosmetic reasons and showed choroidal neurofibroma in most patients and massive retinal gliosis in two patients including the present patient.

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Background

Neurofibromatosis type 1 is characterized by typical skin lesions such as café-au-lait spots and nodular lesions. [1, 2] As one of phacomatoses which show other-organ manifestations in addition to typical skin lesions, neurofibromatosis type 1 shows Lisch iris nodules in ophthalmic examinations as well-known frequent manifestations in the other organs. [3,4,5,6,7,8] Cranial and facial bone defect is also encountered as a rare presentation. Neurofibromatosis type 1 is caused by mutations in the gene NF1 which encodes neurofibromin and plays a role in the regulation of cell proliferation. [9] The absence of neurofibromin or the presence of malfunctioning protein is considered to lead to the proliferation of neurofibroma cells. In the consequences, optic nerve glioma, malignant and benign peripheral nerve sheath tumors, and gastrointestinal stromal tumor are described to develop in patients with neurofibromatosis type 1. [2] Neurofibromatosis type 2 is a different disease entity which is famous for bilateral acoustic (vestibular) nerve schwannoma and is caused by mutations in a different gene, NF2 which encodes merlin. [10, 11]

In this study, we presented an adolescent patient with neurofibromatosis type 1 who underwent enucleation of the phthisic eye and resection of eyelid and orbital neurofibroma lesions on the same side as a cosmetic reason in the 15-year follow-up from the infancy. We showed pathological findings of the phthisic eye in the present patient and also reviewed pathological descriptions of enucleated eyes in 14 patients with neurofibromatosis type 1 in the literature. [12,13,14,15,16,17,18,19,20,21,22,23,24,25]

Case presentation

A 3-year-old boy with the diagnosis of neurofibromatosis type 1 (von Recklinghausen disease) was referred for ophthalmic evaluation during the hospitalization for left orbital mass reduction surgery by orbitozygomatic approach. The visual acuity in decimals with both eyes open was 0.4. He was scared when his right eye was covered, suggestive of poor vision in the left eye. The right eye appeared normal. He had blepharoptosis and proptosis with downward shift of the eye on the left side. The bulbar conjunctiva was edematous and the optic nerve was atrophic in the left eye. He showed eye movement with limitations on the left side. In the past history, he was diagnosed as neurofibromatosis type 1 by many café-au-lait spots of the systemic skin and underwent upper eyelid mass resection on the left side at the age of 1.5 years at a different hospital (Fig. 1A, B, C and D).

Fig. 1
figure 1

Axial views of computed tomographic scan (A, B) and T2-weighted axial views of magnetic resonance imaging (C, D) at the age of 1 year. Note subcutaneous eyelid lesions and orbital lesions on the left side, together with posterior orbital wall defect (arrow in A) and brain parenchymal anomalies of the temporal lobe (arrows in C, D). Axial views of magnetic resonance imaging at 7.5 years (E, T1-weighted image; F, T2-weighted image) and at 8 years (G, T1-weighted image; H, T2-weighted image). Note funnel-shaped total retinal detachment in the left eye (arrows in G, H) which was absent half a year previously (E, F)

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At the age of 5 and 6 years, he underwent three surgeries for orbital mass extirpation on the left side and cranial base reconstruction with titan mesh implantation. At the age of 7 years when he was referred for ophthalmic examinations, the best-corrected visual acuity in decimals was 1.2 in the right eye and 0.02 in the left eye. The intraocular pressure was 16 mmHg in the right eye and 23 mmHg in the left eye. The right eye was normal except for small iris nodules. He showed mydriasis (Fig. 2A) with sluggish light reflex in the left eye. He had lower bulbar conjunctival edema (Fig. 2B), iris nodules (arrow in Fig. 2A), and optic disc atrophy in the left eye. He started to have 0.005% latanoprost eye drops once daily in the left eye. In half a year, he began to show anterior and posterior subcapsular cataract in the left eye (Fig. 2C and D). The intraocular pressure was 15 mmHg in the left eye with latanoprost eye drops. He showed no retinal detachment at that time (Fig. 1E and F). Further half a year later at 8 years old, he showed mature cataract (Fig. 2E and F) in the left eye and ultrasound examination disclosed total retinal detachment in a closed funnel shape (Fig. 2G). Magnetic resonance imaging also showed total retinal detachment in the left eye (arrows in Fig. 1G and H). The left eye became phthisic in a year. He was followed once a year afterwards. At 11 years old, he showed subconjunctival mass lesion in the lower bulbar edematous conjunctiva on the left side (Fig. 2H) which remained stationary for a few years (Fig. 2I).

Fig. 2
figure 2

Slit-lamp photographs in the left eye at the age of 7 years (A, B), showing many iris nodules (arrow in A) and lower bulbar conjunctival lesion (arrow in B). Slit-lamp photographs in the left eye at 7.5 years (C, D), showing mild anterior subcapsular cataract which allows the visualization of fundus to prove no retinal detachment (Fig. 1E and F). Slit-lamp photographs (E, F) and ultrasonography (G) in the left eye at 8 years, showing mature cataract (E, F) and funnel-shaped total retinal detachment (G). Note many iris nodules (arrow in E). Slit-lamp photographs in the left eye at 11.5 years (H) and at 13.5 years (I), showing phthisic eye and enlarging lower bulbar conjunctival lesion (arrows in H, I)

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At 17 years old, he and his family wished to plan a cosmetic surgery before he would graduate from a high school. Computed tomographic scan showed the defective posterior bony orbital wall to the brain parenchyma on the left side (Fig. 3A) with the main mass lesion in the upper eyelid and the downwardly displaced phthisic eye ball (Fig. 3B) on the left side as well as lateral ventricular dilation on both sides (Fig. 3C). Magnetic resonance imaging demonstrated the bulged subdural space with arachnoid fluid collection toward the orbital space on the left side (Fig. 3D and E). The entire orbit and subcutaneous area of the upper eyelid on the left side was occupied with mass lesions and the phthisic eye ball was displaced downwardly. The subconjunctival mass lesion was visible on the lower bulbar conjunctiva (Fig. 3H). The visual acuity in the left eye was no light perception. He was healthy and the physical examinations detected no particular findings. Blood examinations including complete blood cell counts, blood glucose, electrolytes, liver and kidney function tests were all within the normal limits. Urinalysis was also normal. He started to take oral selumetinib (MEK1/2 inhibitor) 80 mg daily.

Fig. 3
figure 3

Axial views of computed tomographic scan at the age of 17 years (A, B, C), showing posterior orbital bone defect (arrow in A) with upper eyelid and orbital mass lesion on the left side, inferiorly dislocated phthisic left eye (B), and dilated lateral ventricles (C). T2-weighted axial views of magnetic resonance imaging at 17 years (D, E), showing upper eyelid mass lesion (arrow in D) and phthisic left eye (arrow in E) with temporal lobe brain parenchymal atrophy on the left side. Slit-lamp photograph half a year later just before the surgery (H), showing phthisic left eye and lower bulbar conjunctival lesion (arrow in H). Macroscopic photographs of enucleated left eye (F, cornea with arrow) and its cut surface (G, optic nerve with arrow), showing total retinal detachment with white tissue filled in the totally detached retinal funnel. Superior to inferior vertical section of optical coherence tomography (I), slit-lamp photograph (J), and wide-field fundus photograph (K) in the right eye at the age of 18 years after the surgery. Note iris nodules (arrows in J) and a suspected choroidal nodule (arrows in I, K) in the right eye

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Half a year later, he underwent enucleation of the phthisic left eye ball and extirpation of the subcutaneous mass lesion together with upper eyelid skin resection. The enucleation was done at first by circumferential cutting of the conjunctiva at the corneal limbus. The sclera and four rectus extraocular muscles showed firm adhesion with the surrounding tissues probably of neurofibromatous lesions. After the blunt dissection of the surrounding tissues which adhered firmly to the sclera and 4 rectus extraocular muscles, the eye ball was extirpated by cutting the 4 rectus muscles at the insertion and then by cutting the optic nerve. The conjunctiva was sutured to make the sac for future insertion of a prosthesis. The skin of the upper eyelid was resected in a crescent shape by an incision line below the eye brow to the lateral side, [26] and the mass was carefully dissected from the pulsating and bulging interface to the presumed dura of the brain. The skin incision was sutured tightly to lift the canthal line on the left side in alignment with the right eye. He showed no operative or postoperative complications. The best-corrected visual acuity in the right eye was 1.2. The right eye showed small iris nodules (arrows in Fig. 3J) and the normal macular structure (Fig. 3I) with a suspected small choroidal nodule (Fig. 3K). The left conjunctival sac was fitted with a prosthetic eye. Family history for neurofibromatosis type 1 was absent. He and his family did not want a genetic testing for NF1.

Pathological findings of the case

The resected orbital and eyelid lesions showed spindle cells with ovoid nuclei and ill-defined eosinophilic cytoplasm which were distributed in diffuse pattern (Fig. 4A and B). Mitotic cells or cells with aberrant nuclei were absent. The spindle cells were positive for S-100 (Fig. 4C) and CD34 (Fig. 4D), and negative for glial fibrillary acidic protein (GFAP, Fig. 4E). All the features were consistent with the diagnosis of neurofibroma.

Fig. 4
figure 4

Subcutaneous left eyelid and orbital mass. Spindle-shaped cells with no aberrant nuclei and ill-defined eosinophilic cytoplasm arranged in diffuse pattern by hematoxylin-eosin stain (A, B). Spindle-shaped cells are positive for S-100 (C) and CD34 (D), negative for glial fibrillary acidic protein (GFAP) (E), consistent with the diagnosis of neurofibroma. Bar = 500 μm in A, and 50 μm in B-E

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The phthisic left eye was enucleated with the intact sclera (Fig. 3F). Macroscopic view of a section of the fixed eye ball showed total retinal detachment in a funnel shape which was filled with white tissue from the optic disc to the posterior border of the calcified lens (Fig. 3G). In hematoxylin-eosin stains, no apparent neurofibroma was noted in the iris, ciliary body (Fig. 5A and B), and choroid (Fig. 5C) while neurofibroma was observed in close contact with the sclera in the episcleral location (Fig. 5B). The neuronal layers of the original retina were observed in a swirling pattern inside the cellular mass which was formed by total retinal detachment (Fig. 5C). The cellular mass of the totally detached retina was fully positive for GFAP (Fig. 6B) while the part of the mass in proximity to the optic nerve was positive for S-100 (Fig. 6C). The other part of the intraocular mass along the choroid appeared more fibrotic (Fig. 6A) and was negative for GFAP (Fig. 6B) and S-100 (Fig. 6C).

Fig. 5
figure 5

Sections of phthisic left eye. No apparent neurofibroma in iris (arrows in A, B) and ciliary body (black asterisks in A, B). Calcified lens (yellow asterisks in A, B) and episcleral neurofibroma (arrowheads in B). A cellular mass lesion involving the swirling detached retina with residual retinal neuronal layers (arrowheads in C). Hematoxylin-eosin stain. Bar = 1000 μm in A and B, and 500 μm in C

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Fig. 6
figure 6

Intraocular mass lesion adjacent to optic nerve (arrow in A) in hematoxylin-eosin stain, positive for glial fibrillary acidic protein (GFAP) (B) and S-100 (C). There is another fibrotic mass lesion along the choroid (asterisks in A, B, C) negative for GFAP (B) and S-100 (C). The optic nerve (arrows in A, B, C) is positive for GFAP (B) and S-100 (C). Bar = 1000 μm in A, B, and C

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Methods of literature review

To analyze similar cases, PubMed and Google Scholar were searched with key words, “neurofibromatosis”, “eye” and “enucleation”. Old literature was collected from references cited in the articles identified during the literature search. The bibliographic database of medical literature in Japanese (Igaku Chuo Zasshi, Ichushi-Web), published by the Japan Medical Abstracts Society (JAMAS, Tokyo, Japan), was also searched with the same key words to get no relevant literature. A sufficient description was found in 14 patients with neurofibromatosis type 1 (Table 1). [12,13,14,15,16,17,18,19,20,21,22,23,24,25]

Table 1 Review of pathological findings of enucleated eyes in 15 patients with neurofibromatosis type 1, including the present patient
Full size table

Results of literature review

The 15 patients with neurofibromatosis type 1 (Table 1), including the present patient, who had pathological examinations of the enucleated eye, were 10 males and 5 females with the age at surgery or autopsy ranging from 1 to 56 (median, 18) years (Table 1). The eye was examined at autopsy in 2 patients (Case 1 and 4) and the other 13 patients underwent enucleation of buphthalmic eyes or phthisic eyes (Case 14, 15) or normally appearing eyes (Case 7, 10) with no vision. One patient (Case 11) lost vision by retinal detachment in the background of choroidal malignant melanoma. Glaucoma of early onset, namely, congenital glaucoma, on the unilateral side was diagnosed in 9 patients. The varying extent of hemifacial neurofibromatosis was observed to involve the eyelid and orbit in 10 patients which roughly overlapped with 9 patients with early-onset glaucoma except for one who lost vision probably by compression optic neuropathy with the orbital mass (Case 7). Systemically, café-au-lait spots were described in 10 patients, multiple skin nodules in 3, and tibial fibrous dysplasia in one (Case 6). The positive family history for neurofibromatosis type 1 was described in 3 patients (Case 11, 12, 14).

Pathologically, neurofibromas in varying extent were found in the choroid of 12 patients. One patient (Case 11) showed choroidal malignant melanoma on the left side and fusiform enlargement of the optic nerve on the right side suspected of optic nerve glioma. In this patient, multiple melanocytic hamartomas were observed in the choroid of the enucleated eye with malignant melanoma. The phthisic eyes in the remaining 2 patients including the present patient (Case 14, 15) showed massive retinal gliosis. Neurofibroma in inferior rectus muscle was described in 2 patients (Case 7, 8).

Discussion

The present patient showed typical features of neurofibromatosis type 1 from birth such as café-au-lait spots and hypertrophic thickened upper eyelid on the left side caused by orbital and eyelid neurofibroma. He was followed by the team of a plastic surgeon, neurosurgeon, and ophthalmologist. The plastic surgeon and neurosurgeon did volume reduction surgeries for orbital and upper eyelid neurofibroma for cosmetic reasons. The vision in the left eye appeared to be poor in childhood due to compression optic neuropathy with orbital neurofibroma. In ophthalmic examinations, he was checked to have normal vision in the right eye and stable condition of the left eye with poor vision. He had no signs of congenital glaucoma: the intraocular pressure in both eyes was within the normal range, and iris ectropion, as a sign of congenital glaucoma in patients with neurofibromatosis type 1, [27] was not noted by slit-lamp examinations in the follow-up.

In the process of 15-year follow-up, he was found to develop mature cataract and total retinal detachment in the left eye at the age of 8 years on the semiannual visit half a year after the previous visit. He did not notice any symptoms in regard to this abrupt change in the left eye. At that time, the reason for the retinal detachment remained basically unknown and would be attributed to incidental blunt trauma to the deviated eye or to suspected intraocular proliferation of neurofibroma. The surgery for the retinal detachment was not recommended because of rather old total retinal detachment in a closed-funnel shape which was revealed by the ultrasound examination. The pathological examinations of the phthisic eye which was enucleated almost 10 years after the development of total retinal detachment showed a mass lesion of massive retinal gliosis [28] involving the detached retina.

Massive retinal gliosis is a concept to show non-neoplastic retinal glial proliferation. [28] Massive retinal gliosis has been described in a case as sequelae to retinal detachment surgery. [29] In another case with the age at 22 months, total retinal detachment has been described in the background of neurofibromatosis type 1. [30] In the present patient, the intraocular mass consisted of two areas from the viewpoint of immunohistochemistry. One area with involvement of the swirled detached retinal tissue was positive for both S-100 and GFAP while the other area along the choroid was negative for both S-100 and GFAP. The area positive for S-100 and GFAP is designated as massive retinal gliosis while the other area negative for S-100 and GFAP is a fibrotic tissue which would be formed by metaplastic retinal pigment epithelial cells or choroidal fibroblasts.

In the enucleated eye of the present patient, no apparent iris, ciliary body or choroidal neurofibromas were found pathologically. The iris ectropion was absent. [27] The episcleral neurofibroma in the patient would be the extension of orbital neurofibromatous lesions which surrounded the enucleated eye ball. The patient did show iris nodules on clinical examinations many years previously when the clear cornea allowed the visualization. The iris nodules would become atrophic in the many-year process of phthisis bulbi. On the visit after the recent surgery, he showed iris nodules as well as a suspected choroidal nodule in the right eye. In the review of other enucleated eyes in patients with neurofibromatosis type 1 which were reported in the literature, choroidal, ciliary body, and iris nodules were most frequent pathological findings (Table 1).

In the review of enucleated eyes in the literature (Table 1), most patients were described to have congenital glaucoma in the unilateral eye, together with the hemifacial lesion which manifested as eyelid or orbital lesion or both lesions of neurofibromatosis on the same side. Their eyes became buphthalmic and painful and lost the vision, leading thus to the enucleation. Most of the enucleated eyes showed choroidal, iris, and ciliary body neurofibroma which would underlie the obstruction of aqueous humor outflow pathway in the iridocorneal angle of the eye. In contrast, the present patient did not develop a buphthalmic eye and he appeared to lose the vision by compression optic neuropathy by the orbital mass lesion with neurofibromatosis. He did show mild increase of intraocular pressure up to 23 mmHg in the left eye when he had already developed optic nerve atrophy. The enucleation of phthisic eye was described only in one patient with neurofibromatosis type 1 (Case 14) in the literature, [25] in addition to the present patient. These 2 patients showed massive retinal gliosis with total retinal detachment as a common pathological feature, suggesting that the phthisis with total retinal detachment would be the background for this pathological presentation.

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References

  1. Bata BM, Hodge DO, Mohney BG. Neurofibromatosis type 1: a population-based study. J Pediatr Ophthalmol Strabismus. 2019;56:243–7.

    Article  PubMed  Google Scholar 

  2. Riccardi VM. Von Recklinghausen neurofibromatosis. N Engl J Med. 1981;305:1617–27.

    Article  CAS  PubMed  Google Scholar 

  3. Lewis RA, Riccardi VM. Von Recklinghausen neurofibromatosis: incidence of iris hamartomata. Ophthalmology. 1981;88:348–54.

    Article  CAS  PubMed  Google Scholar 

  4. Huson S, Jones D, Beck L. Ophthalmic manifestations of neurofibromatosis. Br J Ophthalmol. 1987;71:235–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kinori M, Hodgson N, Zeid JL. Ophthalmic manifestations in neurofibromatosis type 1. Surv Ophthalmol. 2018;63:518–33.

    Article  PubMed  Google Scholar 

  6. Vianna RN, Pacheco DF, Vasconcelos MM, de Laey JJ. Combined hamartoma of the retina and retinal pigment epithelium associated with neurofibromatosis type-1. Int Ophthalmol. 2001;24:63–6.

    Article  CAS  PubMed  Google Scholar 

  7. Destro M, D’Amico DJ, Gragoudas ES, et al. Retinal manifestations of neurofibromatosis: diagnosis and management. Arch Ophthalmol. 1991;109:662–6.

    Article  CAS  PubMed  Google Scholar 

  8. Abdolrahimzadeh B, Piraino DC, Albanese G, Cruciani F, Rahimi S. Neurofibromatosis: an update of ophthalmic characteristics and applications of optical coherence tomography. Clin Ophthalmol. 2016;10:851–60.

    PubMed  PubMed Central  Google Scholar 

  9. Legius E, Brems H. Genetic basis of neurofibromatosis type 1 and related conditions, including mosaicism. Childs Nerv Syst. 2020;36:2285–95.

    Article  PubMed  Google Scholar 

  10. McLaughlin ME, Pepin SM, Maccollin M, Choopong P, Lessell S. Ocular pathologic findings of neurofibromatosis type 2. Arch Ophthalmol. 2007;125:389–94.

    Article  PubMed  Google Scholar 

  11. Ghalavand MA, Asghari A, Farhadi M, et al. The genetic landscape and possible therapeutics of neurofibromatosis type 2. Cancer Cell Int. 2023;23:99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Freeman D. Neurofibroma of the choroid. Arch Ophthalmol. 1934;11:641–5.

    Article  Google Scholar 

  13. Stough JT. Intra-ocular neurofibroma. Arch Ophthalmol. 1937;18:540–6.

    Article  Google Scholar 

  14. Wheeler JM. Plexiform neurofibromatosis (Von Recklinghausen’s disease) involving the choroid, ciliary body, and other structures. Am J Ophthalmol. 1937;20:368–75.

    Article  Google Scholar 

  15. Davis FA. Plexiform neurofibromatosis (Recklinghausen’s disease) of orbit and globe with associated glioma of the optic nerve and brain: report of a case. Arch Ophthalmol. 1939;22:761–91.

    Article  Google Scholar 

  16. Wolter JR, Gonzales-Sirit R, Mankin WJ. Neurofibromatosis of the choroid. Br J Ophthalmol. 1962;54:217–25.

    CAS  Google Scholar 

  17. Hoyt CS, Billson FA. Buphthalmos in neurofibromatosis: is it an expression of regional giantism? J Pediatr Ophthalmol. 1977;14:228–34.

    CAS  PubMed  Google Scholar 

  18. Kobrin JL, Blodi FC, Weingeist TA. Ocular and orbital manifestations of neurofibromatosis. Surv Ophthalmol. 1979;24:45–51.

    Article  CAS  PubMed  Google Scholar 

  19. Kurosawa A, Kurosawa H. Ovoid bodies in choroidal neurofibromatosis. Arch Ophthalmol. 1982;100:1939–41.

    Article  CAS  PubMed  Google Scholar 

  20. Brownstein S, Little JM. Ocular neurofibromatosis. Ophthalmology. 1983;90:1595–9.

    Article  CAS  PubMed  Google Scholar 

  21. Chi JG, Park IA. A case of ocular neurofibromatosis. Korean J Pathol. 1987;21:62–5.

    Google Scholar 

  22. Antle CM, Damji KF, White VA, Rootman J. Uveal malignant melanoma and optic nerve glioma in Von Recklinghausen’s neurofibromatosis. Br J Ophthalmol. 1990;74:502–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Burke JP, Leitch RJ, Talbot JF, Parsons MA. Choroidal neurofibromatosis with congenital iris ectropion and buphthalmos: relationship and significance. J Pediatr Ophthalmol Strabismus. 1991;28:265–7.

    Article  CAS  PubMed  Google Scholar 

  24. Asadi-Amoli F, Ariapad A, Tabatabaei SZ. Enucleation in a patient with neurofibromatosis type 1 with buphthalmos and ocular deformity. Acta Med Iran. 2007;45:515–8.

    Google Scholar 

  25. Jakobiec FA, Rashid A, Lewis K. Massive retinal gliosis in neurofibromatosis type 1. JAMA Ophthalmol. 2015;133:100–2.

    Article  PubMed  Google Scholar 

  26. Alkhairy S, Baig MM. Ocular neurofibromatosis. Cureus. 2021;13:e17765.

    PubMed  PubMed Central  Google Scholar 

  27. Edward DP, Morales J, Bouhenni RA, Patil J, Edward PR, Cummings TJ, Chaudhry IA, Alkatan H. Congenital ectropion uvea and mechanisms of glaucoma in neurofibromatosis type 1: new insights. Ophthalmology. 2012;119:1485–95.

    Article  PubMed  Google Scholar 

  28. Jakobiec FA, Thanos A, Stagner AM, Grossniklaus HE, Proia AD. So-called massive retinal gliosis: a critical review and reappraisal. Surv Ophthalmol. 2016;61:339–56.

    Article  PubMed  Google Scholar 

  29. Gelisken F, Inhoffen W, Rohrbach JM, Bartz-Schmidt KU. Massive retinal gliosis: a late complication of retinal detachment surgery. Graefes Arch Clin Exp Ophthalmol. 2004;242:255–8.

    Article  PubMed  Google Scholar 

  30. Hua HU, Martens R, Read SP, et al. Neurofibromatosis type 1 presenting with retinal detachment and laryngeal plexiform neurofibroma in a toddler. Am J Ophthalmol Case Rep. 2021;23:101170.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama City, 700-8558, Japan

    Toshihiko Matsuo

  2. Department of Ophthalmology, Okayama University Hospital, Okayama City, 700-8558, Japan

    Toshihiko Matsuo

  3. Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama City, 700-8558, Japan

    Kenji Nishida & Takehiro Tanaka

  4. Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama City, 700-8558, Japan

    Takaya Seno & Kiyoshi Yamada

  5. Department of Neurological Surgery, General Medical Center, Kawasaki Medical School, Okayama City, 700-8505, Japan

    Shigeki Ono

  6. Regenerative and Reconstructive Medicine (Ophthalmology), Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Shikata-cho 2-5-1, Okayama City, 700-8558, Japan

    Toshihiko Matsuo

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Contributions

T.M., as an ophthalmologist, followed the patient and did surgery, and wrote the manuscript. K.N. and T.T., as pathologists, made pathological diagnosis. T.S. and K.Y., as plastic surgeons, and S.O., as a neurosurgeon, followed the patient and did surgery. All authors approved the final version of the manuscript.

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Correspondence to Toshihiko Matsuo.

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Matsuo, T., Nishida, K., Tanaka, T. et al. Pathological findings in enucleated eyes of patients with neurofibromatosis type 1: report of a case with 15-year follow-up and review of 14 patients in the literature. BMC Ophthalmol 24, 341 (2024). https://doi.org/10.1186/s12886-024-03604-5

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