Acta Ophthalmologica 2014
for their effort to have performed such wide review on epithelial tumours of the lacrimal gland. Those orbital lesions, in fact, still represent a challenge for both clinicians and researchers. However, some relevant information regarding the pathological features and the prognosis was missed. In the section on pathology and molecular characteristics of those tumours, the authors reported that the immunohistological staining of biomarkers, including the androgen receptor, p53 and the HER-2 ⁄ neu oncoprotein, is strong and diffuses in the malignant area. In this context, it would be important to report even the relation between the expression of apoptosis-related markers and the malignant epithelial tumours of the lachrymal gland (Strianese et al. 2007). Particularly, it was found in a re-examination of the 21 specimens of malignant epithelial tumours of the lacrimal gland that the expression of p53 was directly correlated with the apoptotic index, while expression of Bcl-2 was inversely correlated (Strianese et al. 2007). This expression pattern has been already described in other tumours (Greenblatt et al. 1994). Presumably, the correlation between apoptotic index, p53 and Bcl-2 indicates that tumour cells have lost or down-regulated their survival gene Bcl-2 and up-regulated the expression of p53, to attempt damage repair. Studies on apoptosis and apoptosis-related factors in salivary gland tumours have shown similar correlation as that found in lacrimal gland tumours (Soini et al. 1998). In addition, a statistically significant positive relationship for number of apoptotic cells (TUNEL) and p53, and an inverse correlation for Bcl-2 staining, was demonstrated with overall survival (Strianese et al. 2007). The correlation with survival of apoptotic index, p53 and Bcl-2 expression suggests that the more tumour cells go in apoptosis, up-regulating p53 and down-regulating Bcl-2, the better the survival of patients. As a role of apoptosis regulatory proteins in the pathogenesis of malignant epithelial lacrimal gland tumours was established, the hypothesis that evaluation of the expression of apoptosis-related markers in these tumours may provide a prognostic tool was reported (Strianese et al. 2007). This latter informa-
e80
tion should be mentioned in a review on epithelial tumours of the lacrimal gland, to provide adequate information for the clinician on prognostic factors of those tumours. As these tumours are rare (Bonavolonta` et al. 2013), very little information about the molecular changes leading to their development and progression has so far been reported. Studies on targeting of the apoptosis pathway in epithelial tumours of the lacrimal gland represent an interesting new insight and, indeed, are considered by most researchers the new frontier for the understanding and management of the malignancies (Chaabane et al. 2013). Eventually, this letter may complete the wide review of van Holstein and associates.
References Bonavolonta` G, Strianese D, Grassi P, Comune C, Tranfa F, Uccello G Iuliano A (2013): An analysis of 2,480 space-occupying lesions of the orbit from 1976 to 2011. Ophthal Plast Reconstr Surg 29: 79– 86. Chaabane W, User SD, El-Gazzah M, Jaksik R, Sajjadi E, Rzeszowska-Wolny J & Los MJ (2013): Autophagy, apoptosis, mitoptosis and necrosis: interdependence between those pathways and effects on cancer. Arch Immunol Ther Exp (Warsz) 61: 43–58. Greenblatt MS, Bennet WP & Hollstein M (1994): Mutations in the p53 tumor- suppressor gene, clues to cancer etiology and molecular pathogenesis. Cancer Res 54: 4855–4878. von Holstein SL, Coupland SE, Briscoe D, Le Tourneau C & Heegaard S (2013): Epithelial tumours of the lacrimal gland: a clinical, histopathological, surgical and oncological survey. Acta Ophthalmol 91: 195–206. Soini Y, Tormanern U & Paakko P (1998): Apoptosis is inversely related to bcl-2 but not tobax expression in salivary gland tumors. Histopathology 32: 28–34. Strianese D, Baldi G, Staibano S, Baldi A, De Rosa G, Tranfa F & Bonavolonta` G (2007): Expression of apoptosis-related markers in malignant epithelial tumours of the lacrimal gland and their relation to clinical outcome. Br J Ophthalmol 91: 1239–1243.
Correspondence: Diego Strianese, MD, PhD via Pansini no 5 80131 Naples, Italy
Tel: + 39 081 7462389 Fax: + 39 081 7462389 Email: [email protected]
Intravitreal bevacizumab for the treatment of choroidal metastasis Min Kim,1 Chang Ho Kim,2 Hyoung Jun Koh,1 Sung Chul2 and Sung Soo Kim2 1
Department of Ophthalmology, Institute of Human Barrier Research, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 2 Department of Ophthalmology, Institute of Vision Research, Severance Eye and ENT Hospital, Yonsei University College of Medicine, Seoul, Korea doi: 10.1111/aos.12285
Editor, horoidal metastatic tumour is the most common intraocular malignancy (Shields et al. 1997). In this retrospective case series, we have investigated the efficacy of intravitreal bevacizumab for choroidal metastasis in five eyes of four patients. We evaluated changes in best-corrected visual acuity (BCVA), tumour thickness and resolution of serous retinal detachment on OCT (optical coherence tomography). No patients were receiving any cancerrelated treatment at the time of diagnosis of choroidal metastasis. The mean patient age was 54 years (median 50, range 49–67), and the mean time interval between the diagnosis of primary tumour and choroidal metastasis was 6.8 years (median 4.5 years, range 0– 18). The tumours found in eyes were all solitary. The mean tumour basal diameter was 9.7 mm (median 7.9, range 6.2–13.6), and the mean tumour thickness was 3.8 mm (median 3.2, range 2.9–6.1). Exudative retinal detachment of variable degrees was found in all eyes. A signed informed consent was obtained from all patients undergoing the treatment after discussing the potential risks and benefits of off-label use of intravitreal bevacizumab injection. The study was approved by the institutional review board at Yonsei University Gangnam Severance Hospital. In all eyes, intravitreal bevacizumab was chosen as the primary treatment
C
Acta Ophthalmologica 2014
modality for choroidal metastatic cancer, but all patients also received systemic treatments for non-ocular systemic metastasis after undergoing intravitreal injection. The mean number of injections was 2.6 (median 2.0, range 2–4). 2.5 mg of bevacizumab was administered for tumour thickness >5 mm and extensive exudative retinal detachment. Regression of tumour
with complete resolution of associated exudative retinal detachment occurred in all eyes after an average duration of 2.8 months (median 3, range 2–3) (Fig. 1). The mean preoperative logMAR visual acuity was 0.7 (median 0.7, range 0.3–1.3), and the mean postoperative visual acuity was 0.1 (median 0.2, range 0–0.3). A significant improvement in BCVA was achieved in
(A)
(B) Fig. 1. Large choroidal metastatic tumour with exudative retinal detachment (A) Panoramic photograph at initial presentation displays a large, white to yellowish elevated, dome-shaped choroidal mass at inferior quadrant adjacent to extensive serous retinal detachment which extends to involve the macula. B-scan ultrasonography reveals a large dome-shaped choroidal mass with irregular reflectivity with thickness of 6.1 and 13.6 mm across its base (shown as an inset). Internal reflectivity of variable height is noted. Optical coherence tomography scan at baseline confirms the presence of subretinal fluid (shown as an inset). (B) After three monthly 2.5 mg intravitreal bevacizumab injections, near complete regression of choroidal mass and complete resolution of exudative retinal detachment are noted. There are overlying retinal pigment epithelium colour changes over the previous choroidal tumour location and multiple yellowish subretinal deposits at the previous exudative detachment. The patient’s visual acuity concomitantly improved from 40 ⁄ 200 to 20 ⁄ 30. Optical coherence tomography shows no residual tumour mass or fluid accumulation. At the last follow-up at 12 months, no residual tumour mass or fluid accumulation was observed by indirect ophthalmoscopy, B-scan ultrasonography and OCT scan, and the patient remained tumour-free with restoration of visual acuity to 20 ⁄ 25.
all eyes (p ¼ 0.043, Wilcoxon signed rank test) during the mean follow-up duration of 15 months (median 12, range 12–26). There were no signs of choroidal tumour recurrence at the last follow-up, and no ocular or systemic complications were noted. Our retrospective small case series has shown rapid regression of metastatic tumour and improvement of associated subretinal fluid. Pathogenesis of choroidal metastasis is dependent upon haematogenous spread of the primary malignant tumour, and choroidal metastases have been shown to have hypervascularity (Neudorfer et al. 2011). Tumour growth and choroidal metastasis are thought to be strongly dependent upon VEGF-driven angiogenesis, and the observed reduction in tumour mass and exudation in our study can be attributed to anti-angiogenic and antipermeability effects of bevacizumab on the newly developing tumour vessels (Kuo et al. 2008). Systemic treatments to nonocular metastases, which started after the second injection of each patient, potentially contributed to the favourable response, but it is reasonable to assume that much of the immediate effect observed was attributable to the intravitreal bevacizumab. Compared with conventional chemotherapy and radiotherapy, it is less invasive, can be readily performed in an outpatient setting and can be effective even in cases refractory to conventional treatment (Yao et al. 2009; Lai et al. 2012). It can be safely repeated in the event of tumour recurrence and also used regardless of the tumour location or number of tumours. The finding of our study implicates that intravitreal bevacizumab may be a promising adjunctive and ⁄ or alternative therapeutic option for choroidal metastasis. It may not be the initial treatment of choice at present, but it can be considered an option in patients not responding to conventional systemic therapy in isolated choroidal metastasis or refusing to undergo conventional treatments.
References Kuo IC, Haller JA, Maffrand R, Sambuelli RH & Reviglio VE (2008): Regression of a subfoveal choroidal metastasis of colorectal carcinoma after intravitreous bevacizumab
e81
Acta Ophthalmologica 2014
treatment. Arch Ophthalmol 126: 1311– 1313. Lai CL, Fan KS, Lee YH, Chen HC & Fan WH (2012): Intravitreal administration of bevacizumab in the treatment of choroidal metastasis in a patient with erlotinib-failed pulmonary adenocarcinoma. Lung Cancer 76: 496–498. Neudorfer M, Waisbourd M, Anteby I, Liran A, Goldenberg D, Barak A & Kessler A (2011): Color flow mapping: a non-invasive tool for characterizing and differentiating between uveal melanomas and choroidal metastases. Oncol Rep 25: 91–96. Shields CL, Shields JA, Gross NE, Schwartz GP & Lally SE (1997): Survey of 520 eyes with uveal metastases. Ophthalmology 104: 1265–1276. Yao HY, Horng CT, Chen JT & Tsai ML (2009): Regression of choroidal metastasis secondary to breast carcinoma with adjuvant intravitreal injection of bevacizumab. Acta Ophthalmol Scand 88: e282–e283.
Correspondence: Sung Soo Kim, MD, PhD Department of Ophthalmology Institute of Vision Research Severance Eye and ENT Hospital Yonsei University College of Medicine 134 Shinchon-dong, Seodaemun-gu Seoul, Korea Tel: 82-2-2019-3440 Fax: 82-2-3463-1049 Emails: [email protected]; [email protected]
Prevalence of ectopia lentis and retinal detachment in Marfan syndrome Aman Chandra,1,2 Victoria Ekwalla,1 Anne Child1 and David Charteris2 1
Department of Cardiac and Vascular Sciences, St George’s University of London, London, UK; 2Vitreoretinal Department, Moorfields Eye Hospital, City Road, London, UK doi: 10.1111/aos.12175
Editor,
W
e would like to complement the recent article by Konradsen and Zetterstrom (2013) with results of a survey we undertook. A questionnaire investigating history of ectopia lentis (EL) and retinal detachment (RD) was sent to 567 members of the Marfan Trust (UK) diagnosed with
e82
MFS. One hundred and eighty-five (32.6%) completed questionnaires were returned (Male: 49%, Female: 51%; p = 0.22). The mean age of this cohort was 47 years (M = 48, F = 47). Twenty-eight (15.1%) of respondents reported having had a RD between 1965 and 2011 [M: 17(61%), F: 11(39%)]. The mean age of developing RD was 33 years, occurring earlier in women (25 years) than men (33 years; p = 0.019). Twenty-one percent of those with RD had had previous lens surgery. Forty-four percent of those who had had RD surgery were affected bilaterally, whilst 13 (46%) had recurrence of RD. Fifty-six MFS patients (30.2%) reported having had ectopia lentis (EL) between 1955 and 2011. The mean age for EL diagnosis was 32 years [range 4–64, male mean age: 32 years; female mean age: 16 years (p = 0.549)]. Seventy-five percent of those who had had surgery had bilateral lens surgery. The rate of RD in our cohort is greater, whilst conversely, the rate of EL is lower, than reported by Konradsen and Zetterstrom (2013). The differences may be due to population variation or the age of cohorts (47 versus 39 years). However, both studies lack genetic data. It is known that FBN1 mutations affecting cysteine residues predominate in MFS cases with EL (Faivre et al. 2007). We wonder if other genotype–phenotype relationships exist which may account for differences in ocular manifestations of MFS. We report RD occurring later than previous large studies (Maumenee 1981). It is of interest that women seem to have developed RD earlier than men and is a novel finding not described in MFS, other syndromic nor nonsyndromic RD. Further differences from nonsyndromic RD include the high rate of bilateral RD and recurrent RD. Our figure agrees with previous reports, suggesting recurrence to occur in 30–42% of MFS cases (Nemet et al. 2006). It appears that management of RD in MFS is more complicated with lower success rates than nonsyndromic RD. Twenty-one percentage of patients in our cohort who had had RD had previously had lens surgery, and it appears that EL surgery continues to be a risk for developing RD. With regard to EL, we report it to have been bilateral in 75% of affected
patients. Kondradsen and Zotterstorm did not comment on this, and our figure is higher than in other studies. We believe that this is due to this questionnaire collecting historical data, suggesting that over time, bilateral EL is more common. Although there is no statistical significance between the age of diagnosis of EL and gender, the trend of women being affected younger may need further confirmation. Kondradsen also note that axial length (AL) was not affected by presence of EL. We previously suggested that AL in isolated ectopia lentis may be influenced by causative genetic mutations (Chandra et al. 2012). It would be of interest to know if this were also true with FBN1 mutations. Finally, they also observe that myopia was not as common as the axial lengths would have suggested. We believe that although axial length and myopic correction are closely related, they are not completely mutually exchangeable. It may be worth considering adjusting the Ghent criteria to reflect this. Although there are limitations to questionnaire studies, we believe that our results do provide further valuable insights. Clearer data can only be ascertained from large prospective epidemiological studies. Such a national study of RD in MFS is currently underway through the British Ophthalmic Surveillance Unit (BOSU), and the results will prove interesting.
References Chandra A, Aragon-Martin JA, Hughes K et al. (2012): A genotype-phenotype comparison of ADAMTSL4 and FBN1 in isolated ectopia lentis. Invest Ophthalmol Vis Sci 53: 4889–4896. Faivre L, Collod-Beroud G, Loeys BL et al. (2007): Effect of mutation type and location on clinical outcome in 1,013 probands with Marfan syndrome or related phenotypes and FBN1 mutations: an international study. Am J Hum Genet 81: 454–466. Konradsen TR & Zetterstrom C (2013): A descriptive study of ocular characteristics in Marfan syndrome. Acta Ophthalmol [Epub ahead of print]. Maumenee IH (1981): The eye in the Marfan syndrome. Trans Am Ophthalmol Soc 79: 684–733. Nemet AY, Assia EI, Apple DJ & Barequet IS (2006): Current concepts of ocular manifestations in Marfan syndrome. Surv Ophthalmol 51: 561–575.
Copyright of Acta Ophthalmologica (1755375X) is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
for their effort to have performed such wide review on epithelial tumours of the lacrimal gland. Those orbital lesions, in fact, still represent a challenge for both clinicians and researchers. However, some relevant information regarding the pathological features and the prognosis was missed. In the section on pathology and molecular characteristics of those tumours, the authors reported that the immunohistological staining of biomarkers, including the androgen receptor, p53 and the HER-2 ⁄ neu oncoprotein, is strong and diffuses in the malignant area. In this context, it would be important to report even the relation between the expression of apoptosis-related markers and the malignant epithelial tumours of the lachrymal gland (Strianese et al. 2007). Particularly, it was found in a re-examination of the 21 specimens of malignant epithelial tumours of the lacrimal gland that the expression of p53 was directly correlated with the apoptotic index, while expression of Bcl-2 was inversely correlated (Strianese et al. 2007). This expression pattern has been already described in other tumours (Greenblatt et al. 1994). Presumably, the correlation between apoptotic index, p53 and Bcl-2 indicates that tumour cells have lost or down-regulated their survival gene Bcl-2 and up-regulated the expression of p53, to attempt damage repair. Studies on apoptosis and apoptosis-related factors in salivary gland tumours have shown similar correlation as that found in lacrimal gland tumours (Soini et al. 1998). In addition, a statistically significant positive relationship for number of apoptotic cells (TUNEL) and p53, and an inverse correlation for Bcl-2 staining, was demonstrated with overall survival (Strianese et al. 2007). The correlation with survival of apoptotic index, p53 and Bcl-2 expression suggests that the more tumour cells go in apoptosis, up-regulating p53 and down-regulating Bcl-2, the better the survival of patients. As a role of apoptosis regulatory proteins in the pathogenesis of malignant epithelial lacrimal gland tumours was established, the hypothesis that evaluation of the expression of apoptosis-related markers in these tumours may provide a prognostic tool was reported (Strianese et al. 2007). This latter informa-
e80
tion should be mentioned in a review on epithelial tumours of the lacrimal gland, to provide adequate information for the clinician on prognostic factors of those tumours. As these tumours are rare (Bonavolonta` et al. 2013), very little information about the molecular changes leading to their development and progression has so far been reported. Studies on targeting of the apoptosis pathway in epithelial tumours of the lacrimal gland represent an interesting new insight and, indeed, are considered by most researchers the new frontier for the understanding and management of the malignancies (Chaabane et al. 2013). Eventually, this letter may complete the wide review of van Holstein and associates.
References Bonavolonta` G, Strianese D, Grassi P, Comune C, Tranfa F, Uccello G Iuliano A (2013): An analysis of 2,480 space-occupying lesions of the orbit from 1976 to 2011. Ophthal Plast Reconstr Surg 29: 79– 86. Chaabane W, User SD, El-Gazzah M, Jaksik R, Sajjadi E, Rzeszowska-Wolny J & Los MJ (2013): Autophagy, apoptosis, mitoptosis and necrosis: interdependence between those pathways and effects on cancer. Arch Immunol Ther Exp (Warsz) 61: 43–58. Greenblatt MS, Bennet WP & Hollstein M (1994): Mutations in the p53 tumor- suppressor gene, clues to cancer etiology and molecular pathogenesis. Cancer Res 54: 4855–4878. von Holstein SL, Coupland SE, Briscoe D, Le Tourneau C & Heegaard S (2013): Epithelial tumours of the lacrimal gland: a clinical, histopathological, surgical and oncological survey. Acta Ophthalmol 91: 195–206. Soini Y, Tormanern U & Paakko P (1998): Apoptosis is inversely related to bcl-2 but not tobax expression in salivary gland tumors. Histopathology 32: 28–34. Strianese D, Baldi G, Staibano S, Baldi A, De Rosa G, Tranfa F & Bonavolonta` G (2007): Expression of apoptosis-related markers in malignant epithelial tumours of the lacrimal gland and their relation to clinical outcome. Br J Ophthalmol 91: 1239–1243.
Correspondence: Diego Strianese, MD, PhD via Pansini no 5 80131 Naples, Italy
Tel: + 39 081 7462389 Fax: + 39 081 7462389 Email: [email protected]
Intravitreal bevacizumab for the treatment of choroidal metastasis Min Kim,1 Chang Ho Kim,2 Hyoung Jun Koh,1 Sung Chul2 and Sung Soo Kim2 1
Department of Ophthalmology, Institute of Human Barrier Research, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 2 Department of Ophthalmology, Institute of Vision Research, Severance Eye and ENT Hospital, Yonsei University College of Medicine, Seoul, Korea doi: 10.1111/aos.12285
Editor, horoidal metastatic tumour is the most common intraocular malignancy (Shields et al. 1997). In this retrospective case series, we have investigated the efficacy of intravitreal bevacizumab for choroidal metastasis in five eyes of four patients. We evaluated changes in best-corrected visual acuity (BCVA), tumour thickness and resolution of serous retinal detachment on OCT (optical coherence tomography). No patients were receiving any cancerrelated treatment at the time of diagnosis of choroidal metastasis. The mean patient age was 54 years (median 50, range 49–67), and the mean time interval between the diagnosis of primary tumour and choroidal metastasis was 6.8 years (median 4.5 years, range 0– 18). The tumours found in eyes were all solitary. The mean tumour basal diameter was 9.7 mm (median 7.9, range 6.2–13.6), and the mean tumour thickness was 3.8 mm (median 3.2, range 2.9–6.1). Exudative retinal detachment of variable degrees was found in all eyes. A signed informed consent was obtained from all patients undergoing the treatment after discussing the potential risks and benefits of off-label use of intravitreal bevacizumab injection. The study was approved by the institutional review board at Yonsei University Gangnam Severance Hospital. In all eyes, intravitreal bevacizumab was chosen as the primary treatment
C
Acta Ophthalmologica 2014
modality for choroidal metastatic cancer, but all patients also received systemic treatments for non-ocular systemic metastasis after undergoing intravitreal injection. The mean number of injections was 2.6 (median 2.0, range 2–4). 2.5 mg of bevacizumab was administered for tumour thickness >5 mm and extensive exudative retinal detachment. Regression of tumour
with complete resolution of associated exudative retinal detachment occurred in all eyes after an average duration of 2.8 months (median 3, range 2–3) (Fig. 1). The mean preoperative logMAR visual acuity was 0.7 (median 0.7, range 0.3–1.3), and the mean postoperative visual acuity was 0.1 (median 0.2, range 0–0.3). A significant improvement in BCVA was achieved in
(A)
(B) Fig. 1. Large choroidal metastatic tumour with exudative retinal detachment (A) Panoramic photograph at initial presentation displays a large, white to yellowish elevated, dome-shaped choroidal mass at inferior quadrant adjacent to extensive serous retinal detachment which extends to involve the macula. B-scan ultrasonography reveals a large dome-shaped choroidal mass with irregular reflectivity with thickness of 6.1 and 13.6 mm across its base (shown as an inset). Internal reflectivity of variable height is noted. Optical coherence tomography scan at baseline confirms the presence of subretinal fluid (shown as an inset). (B) After three monthly 2.5 mg intravitreal bevacizumab injections, near complete regression of choroidal mass and complete resolution of exudative retinal detachment are noted. There are overlying retinal pigment epithelium colour changes over the previous choroidal tumour location and multiple yellowish subretinal deposits at the previous exudative detachment. The patient’s visual acuity concomitantly improved from 40 ⁄ 200 to 20 ⁄ 30. Optical coherence tomography shows no residual tumour mass or fluid accumulation. At the last follow-up at 12 months, no residual tumour mass or fluid accumulation was observed by indirect ophthalmoscopy, B-scan ultrasonography and OCT scan, and the patient remained tumour-free with restoration of visual acuity to 20 ⁄ 25.
all eyes (p ¼ 0.043, Wilcoxon signed rank test) during the mean follow-up duration of 15 months (median 12, range 12–26). There were no signs of choroidal tumour recurrence at the last follow-up, and no ocular or systemic complications were noted. Our retrospective small case series has shown rapid regression of metastatic tumour and improvement of associated subretinal fluid. Pathogenesis of choroidal metastasis is dependent upon haematogenous spread of the primary malignant tumour, and choroidal metastases have been shown to have hypervascularity (Neudorfer et al. 2011). Tumour growth and choroidal metastasis are thought to be strongly dependent upon VEGF-driven angiogenesis, and the observed reduction in tumour mass and exudation in our study can be attributed to anti-angiogenic and antipermeability effects of bevacizumab on the newly developing tumour vessels (Kuo et al. 2008). Systemic treatments to nonocular metastases, which started after the second injection of each patient, potentially contributed to the favourable response, but it is reasonable to assume that much of the immediate effect observed was attributable to the intravitreal bevacizumab. Compared with conventional chemotherapy and radiotherapy, it is less invasive, can be readily performed in an outpatient setting and can be effective even in cases refractory to conventional treatment (Yao et al. 2009; Lai et al. 2012). It can be safely repeated in the event of tumour recurrence and also used regardless of the tumour location or number of tumours. The finding of our study implicates that intravitreal bevacizumab may be a promising adjunctive and ⁄ or alternative therapeutic option for choroidal metastasis. It may not be the initial treatment of choice at present, but it can be considered an option in patients not responding to conventional systemic therapy in isolated choroidal metastasis or refusing to undergo conventional treatments.
References Kuo IC, Haller JA, Maffrand R, Sambuelli RH & Reviglio VE (2008): Regression of a subfoveal choroidal metastasis of colorectal carcinoma after intravitreous bevacizumab
e81
Acta Ophthalmologica 2014
treatment. Arch Ophthalmol 126: 1311– 1313. Lai CL, Fan KS, Lee YH, Chen HC & Fan WH (2012): Intravitreal administration of bevacizumab in the treatment of choroidal metastasis in a patient with erlotinib-failed pulmonary adenocarcinoma. Lung Cancer 76: 496–498. Neudorfer M, Waisbourd M, Anteby I, Liran A, Goldenberg D, Barak A & Kessler A (2011): Color flow mapping: a non-invasive tool for characterizing and differentiating between uveal melanomas and choroidal metastases. Oncol Rep 25: 91–96. Shields CL, Shields JA, Gross NE, Schwartz GP & Lally SE (1997): Survey of 520 eyes with uveal metastases. Ophthalmology 104: 1265–1276. Yao HY, Horng CT, Chen JT & Tsai ML (2009): Regression of choroidal metastasis secondary to breast carcinoma with adjuvant intravitreal injection of bevacizumab. Acta Ophthalmol Scand 88: e282–e283.
Correspondence: Sung Soo Kim, MD, PhD Department of Ophthalmology Institute of Vision Research Severance Eye and ENT Hospital Yonsei University College of Medicine 134 Shinchon-dong, Seodaemun-gu Seoul, Korea Tel: 82-2-2019-3440 Fax: 82-2-3463-1049 Emails: [email protected]; [email protected]
Prevalence of ectopia lentis and retinal detachment in Marfan syndrome Aman Chandra,1,2 Victoria Ekwalla,1 Anne Child1 and David Charteris2 1
Department of Cardiac and Vascular Sciences, St George’s University of London, London, UK; 2Vitreoretinal Department, Moorfields Eye Hospital, City Road, London, UK doi: 10.1111/aos.12175
Editor,
W
e would like to complement the recent article by Konradsen and Zetterstrom (2013) with results of a survey we undertook. A questionnaire investigating history of ectopia lentis (EL) and retinal detachment (RD) was sent to 567 members of the Marfan Trust (UK) diagnosed with
e82
MFS. One hundred and eighty-five (32.6%) completed questionnaires were returned (Male: 49%, Female: 51%; p = 0.22). The mean age of this cohort was 47 years (M = 48, F = 47). Twenty-eight (15.1%) of respondents reported having had a RD between 1965 and 2011 [M: 17(61%), F: 11(39%)]. The mean age of developing RD was 33 years, occurring earlier in women (25 years) than men (33 years; p = 0.019). Twenty-one percent of those with RD had had previous lens surgery. Forty-four percent of those who had had RD surgery were affected bilaterally, whilst 13 (46%) had recurrence of RD. Fifty-six MFS patients (30.2%) reported having had ectopia lentis (EL) between 1955 and 2011. The mean age for EL diagnosis was 32 years [range 4–64, male mean age: 32 years; female mean age: 16 years (p = 0.549)]. Seventy-five percent of those who had had surgery had bilateral lens surgery. The rate of RD in our cohort is greater, whilst conversely, the rate of EL is lower, than reported by Konradsen and Zetterstrom (2013). The differences may be due to population variation or the age of cohorts (47 versus 39 years). However, both studies lack genetic data. It is known that FBN1 mutations affecting cysteine residues predominate in MFS cases with EL (Faivre et al. 2007). We wonder if other genotype–phenotype relationships exist which may account for differences in ocular manifestations of MFS. We report RD occurring later than previous large studies (Maumenee 1981). It is of interest that women seem to have developed RD earlier than men and is a novel finding not described in MFS, other syndromic nor nonsyndromic RD. Further differences from nonsyndromic RD include the high rate of bilateral RD and recurrent RD. Our figure agrees with previous reports, suggesting recurrence to occur in 30–42% of MFS cases (Nemet et al. 2006). It appears that management of RD in MFS is more complicated with lower success rates than nonsyndromic RD. Twenty-one percentage of patients in our cohort who had had RD had previously had lens surgery, and it appears that EL surgery continues to be a risk for developing RD. With regard to EL, we report it to have been bilateral in 75% of affected
patients. Kondradsen and Zotterstorm did not comment on this, and our figure is higher than in other studies. We believe that this is due to this questionnaire collecting historical data, suggesting that over time, bilateral EL is more common. Although there is no statistical significance between the age of diagnosis of EL and gender, the trend of women being affected younger may need further confirmation. Kondradsen also note that axial length (AL) was not affected by presence of EL. We previously suggested that AL in isolated ectopia lentis may be influenced by causative genetic mutations (Chandra et al. 2012). It would be of interest to know if this were also true with FBN1 mutations. Finally, they also observe that myopia was not as common as the axial lengths would have suggested. We believe that although axial length and myopic correction are closely related, they are not completely mutually exchangeable. It may be worth considering adjusting the Ghent criteria to reflect this. Although there are limitations to questionnaire studies, we believe that our results do provide further valuable insights. Clearer data can only be ascertained from large prospective epidemiological studies. Such a national study of RD in MFS is currently underway through the British Ophthalmic Surveillance Unit (BOSU), and the results will prove interesting.
References Chandra A, Aragon-Martin JA, Hughes K et al. (2012): A genotype-phenotype comparison of ADAMTSL4 and FBN1 in isolated ectopia lentis. Invest Ophthalmol Vis Sci 53: 4889–4896. Faivre L, Collod-Beroud G, Loeys BL et al. (2007): Effect of mutation type and location on clinical outcome in 1,013 probands with Marfan syndrome or related phenotypes and FBN1 mutations: an international study. Am J Hum Genet 81: 454–466. Konradsen TR & Zetterstrom C (2013): A descriptive study of ocular characteristics in Marfan syndrome. Acta Ophthalmol [Epub ahead of print]. Maumenee IH (1981): The eye in the Marfan syndrome. Trans Am Ophthalmol Soc 79: 684–733. Nemet AY, Assia EI, Apple DJ & Barequet IS (2006): Current concepts of ocular manifestations in Marfan syndrome. Surv Ophthalmol 51: 561–575.
Copyright of Acta Ophthalmologica (1755375X) is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
