Periorbital Fat Atrophy — An Unfamiliar Side Effect of Prostaglandin Analogues

Jayaprakasam, Anuradha; Ghazi-Nouri, Seyed

doi:10.3109/01676830.2010.527028

Cited by 83 publications

(76 citation statements)

References 8 publications

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“…We would predict that the drug will reach the retro-orbital space to exert its intended effect, since topical ocular administration of PGF 2a leads to its detection in the aqueous humor and systemic circulation (35,36); the existence of reduced periorbital fat in bimatoprost-treated patients also supports the prediction (8).…”

Section: Discussionmentioning

confidence: 89%

“…The enophthalmos in people treated with eye drops containing PGF 2a for glaucoma (2-7) has been suggested to be caused by fat atrophy (8). With this in mind, we have investigated whether the reduced orbital fat volume is the result of diminished proliferation, inhibition of adipogenesis, and/or increased lipolysis.…”

Section: Discussionmentioning

confidence: 99%

“…This effect can be reversed by discontinuation of the prostaglandin analog therapy. A possible mechanism by which PGF 2a agonists might produce enophthalmos is through reduction of orbital fat volume (8). A PGF 2a receptor agonist has been shown to be a potent inhibitor of adipose differentiation in newborn rat precursor cells (9).…”

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confidence: 99%

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Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Draman

Grennan-Jones²,

Zhang³

et al. 2013

Thyroid

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Background: In Graves' orbitopathy (GO), increased proliferation, excess adipogenesis, and hyaluronan overproduction produce GO exophthalmos. Enophthalmos occurs in some glaucoma patients treated with Bimatoprost (prostaglandin F 2a , PGF 2a ) eye drops. We hypothesized that enophthalmos is secondary to reductions in orbital tissue proliferation, adipogenesis, and/or increased lipolysis. We aimed to determine which of these is affected by PGF 2a by using the 3T3-L1 murine preadipocyte cell line and primary human orbital fibroblasts (OFs) from GO patients (n = 5) and non-GO (n = 5). Methods: 3T3-L1 cells and orbital OFs were cultured alone or with PGF 2a (all experiments used 10 -8 to 10 -6 M) and counted on days 1/2/3 or 5, respectively; cell cycle analysis (flow cytometry) was applied. Adipogenesis (in the presence/absence of PGF 2a ) was evaluated (day 7 or 15 for 3T3-L1 and primary cells, respectively) morphologically by Oil Red O staining and quantitative polymerase chain reaction measurement of adipogenesis markers (glycerol-3-phosphate dehydrogenase and lipoprotein lipase, respectively). For lipolysis, in vitrodifferentiated 3T3-L1 or mature orbital adipocytes were incubated with norepinephrine and PGF 2a and free glycerol was assayed. Appropriate statistical tests were applied. Results: The population doubling time of 3T3-L1 was 27.3 -1.4 hours-significantly increased by dimethyl sulfoxide 0.02% to 44.6 -4.8 hours ( p = 0.007) and further significantly increased ( p = 0.049 compared with dimethyl sulfoxide) by 10 -8 M PGF 2a to 93.6 -19.0 hours, indicating reduced proliferation, which was caused by prolongation of G2/M. GO OFs proliferated significantly more rapidly than non-GO (population doubling time 5.36 -0.34 or 6.63 -0.35 days, respectively, p = 0.035), but the proliferation of both was significantly reduced (dose dependent from 10 -8 M) by PGF 2a , again with prolongation of G2/M. Adipogenesis in 3T3-L1 cells was minimally affected by PGF 2a when assessed morphologically, but the drug significantly reduced transcripts of the glycerol-3-phosphate dehydrogenase differentiation marker. GO OFs displayed significantly higher adipogenic potential than non-GO, but in both populations, adipogenesis, evaluated by all 3 methods, was significantly reduced (dose dependent from 10 -8 M) by PGF 2a . There was no effect of PGF 2a on basal or norepinephrine-induced lipolysis, in 3T3-L1 or human OFs, either GO or non-GO.Conclusions: The results demonstrate that PGF 2a significantly reduces proliferation and adipogenesis and that human OFs are more sensitive to its effects than 3T3-L1. Consequently, PGF 2a could be effective in the treatment of GO.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Draman

Grennan-Jones²,

Zhang³

et al. 2013

Thyroid

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“…Local adverse events, however, such as iris-pigmentation, increasing eyelash growth, or conjunctival hyperemia, are well recognized [1]. Recently, deepening of the upper eyelid sulcus (DUES) associated with the use of bimatoprost or travoprost has also been reported as a side effect [2][3][4][5][6][7]. Interestingly, in cases treated with the PG analog latanoprost, DUES has not been reported in over 10 years of clinical use, although the incidence of DUES in latanoprost-treated patients has not been denied.…”

Section: Introductionmentioning

confidence: 99%

Incidence of deepening of the upper eyelid sulcus after switching from latanoprost to bimatoprost

Aihara

Shirato²,

Sakata

2011

Jpn J Ophthalmol

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Purpose To investigate the incidence of deepening of the upper eyelid sulcus (DUES) after use of bimatoprost in Japanese glaucoma patients. Methods Twenty-five open-angle glaucoma Japanese patients treated with latanoprost in both eyes for 6 months or longer and needing further intraocular pressure (IOP) reduction were enrolled prospectively. Latanoprost was switched to bimatoprost, and the patients were observed at 1, 3, and 6 months. The patients were queried for the presence of DUES at every visit. Sex, refraction, and IOP were evaluated as related factors. The photographs of the eyes and forehead taken at each of the four visits were randomly displayed and judged for the presence of DUES with unanimous confirmation by three examiners. Results One month after the switch to bimatoprost, 44% (11/25) of the patients had DUES, including three with unilateral DUES. At 3 and 6 months, 60% (15/25) of the patients had DUES. The incidence was significantly higher in older patients and nonmyopic eyes (P \ 0.01), but not related to sex or IOP reduction. Finally, 53.3% (8/15) of the patients objectively judged to have DUES noticed the presence of DUES by themselves. Only one patient dropped out of the study because of DUES (after 3 months). Conclusion DUES is an often-observed side effect of bimatoprost topical treatment in Japanese glaucoma patients.

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“…However, there are recent reports of deepening of the eyelid superior sulcus after long-term instillation of topical prostaglandin analogs that was recovered by discontinuation of the topical prostaglandin therapy, [11][12][13][14][15][16][17][18][19][20] and some of these patients have shown enophthalmos combined with superior sulcus deepening. [14][15][16]20 This recently recognized complication causes a disparity in the appearance of the eyelids and could be a reason for stopping glaucoma drug therapy.…”

Section: Discussionmentioning

confidence: 99%

1258 In Vitro study of Anti-adipogenic Profile of Latanoprost, Travoprost, Bimatoprost and Tafluprost in Human Orbital Preadiopocytes

Jung

Choi

Lee

et al. 2012

SciVee

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Purpose: To investigate the effect of prostaglandin F2a (PGF2a), latanoprost, travoprost, bimatoprost, and tafluprost on human orbital preadipocyte differentiation and intracellular lipid storage, and to reveal the potential mechanisms by which topical prostaglandin analogs induce orbital fat volume reduction and cause deep superior sulcus syndrome. Methods: Human orbital adipose precursors were treated in vitro for 24 h (day 1) with PGF2a, latanoprost, travoprost, bimatoprost, and tafluprost in their commercial formulations (1:100 dilution). Expressions of adipogenic transcription factor, peroxisome proliferator-activated receptor-gamma (PPARg), and CCAATenhancer-binding protein a (C/EBPa) were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) at day 7. At 14 days, cells were stained with oil red O, intracellular lipid accumulation was evaluated by lipid absorbance, and adipocyte expression marker [Lipoprotein lipase (LPL)] was determined by real-time RT-PCR. Results: Our results showed that PGF2a and topical prostaglandin analogs down-regulated the expression of PPARg and C/EBPa, and inhibited accumulation of intra-cytoplasmic lipid droplets and expression of LPL compared with the untreated control. Comparison between the 4 drugs showed that latanoprost had the weakest antiadipogenic effect, and bimatoprost induced the most significant reduction of adipogenesis. Conclusion: Latanoprost, travoprost, bimatoprost, and tafluprost inhibited human preadipocyte differentiation and intracellular lipid accumulation. Morphologic and metabolic changes in orbital adipocytes caused by PGF2a analogs are a possible pathophysiologic explanation of superior eyelid deepening in patients with glaucoma.

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Periorbital Fat Atrophy — An Unfamiliar Side Effect of Prostaglandin Analogues

Cited by 83 publications

References 8 publications

Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Incidence of deepening of the upper eyelid sulcus after switching from latanoprost to bimatoprost

1258 In Vitro study of Anti-adipogenic Profile of Latanoprost, Travoprost, Bimatoprost and Tafluprost in Human Orbital Preadiopocytes

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Periorbital Fat Atrophy — An Unfamiliar Side Effect of Prostaglandin Analogues

Cited by 83 publications

References 8 publications

Effects of Prostaglandin F2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Effects of Prostaglandin F2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Incidence of deepening of the upper eyelid sulcus after switching from latanoprost to bimatoprost

1258 In Vitro study of Anti-adipogenic Profile of Latanoprost, Travoprost, Bimatoprost and Tafluprost in Human Orbital Preadiopocytes

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Product

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Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy