Ranibizumab for the management of Sorsby fundus dystrophy

Balaskas, Konstantinos; Hovan, Marta; Mahmood, Sajjad; Bishop, Paul N.

doi:10.1038/eye.2012.221

Cited by 19 publications

(20 citation statements)

References 5 publications

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“…Consistent with previous reports, 19,[56][57][58][59] monotherapy with intravitreal injections of VEGF-inhibitors was beneficial in all three eyes treated for fovea-involving CNV. Because extrafoveal CNV has been shown to extend subfoveally, resulting in substantial visual decline if left untreated, 10 but also after laser photocoagulation, 60 we treated an asymptomatic eccentric PCV also.…”

Section: Therapeutic Approachessupporting

confidence: 91%

Sorsby Fundus Dystrophy: Novel Mutations, Novel Phenotypic Characteristics, and Treatment Outcomes

Gliem

Müller

Mangold

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Section: Therapeutic Approachessupporting

confidence: 91%

Sorsby Fundus Dystrophy: Novel Mutations, Novel Phenotypic Characteristics, and Treatment Outcomes

Gliem

Müller

Mangold

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…Inhibition of vascular endothelial growth factor (VEGF) with monoclonal antibodies has been shown to be an effective treatment, delaying visual loss due to CNV and reducing scarring (Gemenetzi et al, 2011;Gliem et al, 2015;Keller et al, 2014). Bevacizumab (Avastin) or less commonly ranibizumab (Lucentis) have shown moderate benefits when administered systemically but are more effective and safer when administered intravitreally (Balaskas et al, 2012;Gemenetzi et al, 2011;Keller et al, 2014). Some studies suggest the addition of a longacting angiostatic steroid, in combination with bevacizumab, has beneficial effects due to the aggressive nature of CNV and its early onset (Sivaprasad et al, 2008).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Sorsby fundus dystrophy – A review of pathology and disease mechanisms

Christensen

Brown

Cree

et al. 2017

Experimental Eye Research

143

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Sorsby fundus dystrophy (SFD) is an autosomal dominant macular dystrophy with an estimated prevalence of 1 in 220,000 and an onset of disease around the 4th to 6th decade of life. Similar to age-related macular degeneration (AMD), ophthalmoscopy reveals accumulation of protein/lipid deposits under the retinal pigment epithelium (RPE), referred to as drusen, in the eyes of patients with SFD. SFD is caused by variants in the gene for tissue inhibitor of metalloproteinases-3 (TIMP3), which has been found in drusen-like deposits of SFD patients. TIMP3 is constitutively expressed by RPE cells and, in healthy eyes, resides in Bruch's membrane. Most SFD-associated TIMP3 variants involve the gain or loss of a cysteine residue. This suggests the protein aberrantly forms intermolecular disulphide bonds, resulting in the formation of TIMP3 dimers. It has been demonstrated that SFD-associated TIMP3 variants are more resistant to turnover, which is thought to be a result of dimerisation and thought to explain the accumulation of TIMP3 in drusen-like deposits at the level of Bruch's membrane. An important function of TIMP3 within the outer retina is to regulate the thickness of Bruch's membrane. TIMP3 performs this function by inhibiting the activity of matrix metalloproteinases (MMPs), which have the function of catalysing breakdown of the extracellular matrix. TIMP3 has an additional function to inhibit vascular endothelial growth factor (VEGF) signalling and thereby to inhibit angiogenesis. However, it is unclear whether SFD-associated TIMP3 variant proteins retain these functions. In this review, we discuss the current understanding of the potential mechanisms underlying development of SFD and summarise all known SFD-associated TIMP3 variants. Cell culture models provide an invaluable way to study disease and identify potential treatments. These allow a greater understanding of RPE physiology and pathophysiology, including the ability to study the blood-retinal barrier as well as other RPE functions such as phagocytosis of photoreceptor outer segments. This review describes some examples of such recent in vitro studies and how they might provide new insights into degenerative diseases like SFD. Thus far, most studies on SFD have been performed using ARPE-19 cells or other, less suitable, cell-types. Now, induced pluripotent stem cell (iPSC) technologies allow the possibility to non-invasively collect somatic cells, such as dermal fibroblast cells and reprogram those to produce iPSCs. Subsequent differentiation of iPSCs can generate patient-derived RPE cells that carry the same disease-associated variant as RPE cells in the eyes of the patient. Use of these patient-derived RPE cells in novel cell culture systems should increase our understanding of how SFD and similar macular dystrophies develop.

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“…An early study reported resolution of active CNVM in an SFD patient in response to a series of systemic infusions of bevacizumab (Prager, Michels, Geitzenauer, & Schmidt‐Erfurth, ). Intravitreal injections of bevacizumab and ranibizumab have been reported to be successful in the treatment of active CNVM in SFD patients (Balaskas, Hovan, Mahmood, & Bishop, ; Fung, Stohr, Weber, Holz, & Yannuzzi, ; Gemenetzi, Luff, & Lotery, ; Gliem et al, ; Gray, Wong, & Raymond, ; Kapoor & Bakri, ; Menassa et al, ). Early CNVM detection and treatment with anti‐VEGF agents result in improved visual prognosis and reduced subretinal scarring and is now considered the mainstay of SFD treatment (Keller et al, ; Menassa et al, ).…”

Section: Clinical Diseasementioning

confidence: 99%

“…An early study reported resolution of active CNVM in an SFD patient in response to a series of systemic infusions of bevacizumab (Prager, Michels, Geitzenauer, & Schmidt-Erfurth, 2007). Intravitreal injections of bevacizumab and ranibizumab have been reported to be successful in the treatment of active CNVM in SFD patients (Balaskas, Hovan, Mahmood, & Bishop, 2013;Fung, Stohr, Weber, Holz, & Yannuzzi, 2013;Gemenetzi, Luff, & Lotery, 2011;Gliem, Muller, Mangold, Holz, et al, 2015 and is now considered the mainstay of SFD treatment (Keller et al, 2015;Menassa et al, 2017). The frequency of CNVM recurrences is variable, and no particular treatment protocol has been studied.…”

Section: Treatmentmentioning

confidence: 99%

Sorsby fundus dystrophy: Insights from the past and looking to the future

Anand‐Apte

Chao

Singh

et al. 2018

J of Neuroscience Research

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Sorsby fundus dystrophy (SFD), an autosomal dominant, fully penetrant, degenerative disease of the macula, is manifested by symptoms of night blindness or sudden loss of visual acuity, usually in the third to fourth decades of life due to choroidal neovascularization (CNV). SFD is caused by specific mutations in the Tissue Inhibitor of Metalloproteinase-3, (TIMP3) gene. The predominant histo-pathological feature in the eyes of patients with SFD are confluent 20-30 m thick, amorphous deposits found between the basement membrane of the retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch's membrane. SFD is a rare disease but it has generated significant interest because it closely resembles the exudative or "wet" form of the more common age-related macular degeneration (AMD). In addition, in both SFD and AMD donor eyes, sub-retinal deposits have been shown to accumulate TIMP3 protein. Understanding the molecular functions of wild-type and mutant TIMP3 will provide significant insights into the patho-physiology of SFD and perhaps AMD. This review summarizes the current knowledge on TIMP3 and how mutations in TIMP3 cause SFD to provide insights into how we can study this disease going forward. Findings from these studies could have potential therapeutic implications for both SFD and AMD.

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Ranibizumab for the management of Sorsby fundus dystrophy

Cited by 19 publications

References 5 publications

Sorsby Fundus Dystrophy: Novel Mutations, Novel Phenotypic Characteristics, and Treatment Outcomes

Sorsby Fundus Dystrophy: Novel Mutations, Novel Phenotypic Characteristics, and Treatment Outcomes

Sorsby fundus dystrophy – A review of pathology and disease mechanisms

Sorsby fundus dystrophy: Insights from the past and looking to the future

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