The Open Ophthalmology Journal




ISSN: 1874-3641 ― Volume 14, 2020

Presumed Pyogenic Granuloma Associated with Intravitreal Anti-Vascular Endothelial Growth Factor Therapy



Jesse J Jung 1, 2, Kara E Della Torre 1, 2, 3, Millie R Fell 1, Christopher C Teng 1, 4, K Bailey Freund*, 1, 2, 3, 5
1 Department of Ophthalmology, New York University School of Medicine, New York, NY, USA
2 LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Institute, New York, NY, USA
3 Vitreous, Retina, Macula Consultants of New York, New York, NY, USA
4 Einhorn Clinical Research Center, The New York Eye and Ear Infirmary, New York, NY, USA
5 Edward S. Harkness Eye Institute, Columbia University College of Physicians and Surgeons, New York, NY, USA

Abstract

To report a case of a presumed pyogenic granuloma at the site of multiple intravitreal anti-Vascular Endothelial Growth Factor (VEGF) injections. Intravitreal anti-VEGF injections can be complicated by a localized reaction of the conjunctiva.

Keywords: Ranibizumab (Lucentis), age-related macular degeneration, pyogenic granuloma, nodule, inflammation.


Article Information


Identifiers and Pagination:

Year: 2011
Volume: 5
First Page: 59
Last Page: 62
Publisher Id: TOOPHTJ-5-59
DOI: 10.2174/1874364101105010059

Article History:

Received Date: 12/5/2011
Revision Received Date: 30/7/2011
Acceptance Date: 16/9/2011
Electronic publication date: 19/12/2011
Collection year: 2011

© Jung et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http: //creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.


* Address correspondence to this author at the 460 Park Avenue, Fifth Floor, New York, NY 10022, USA; Tel: 212-861-9797; Fax: 212-628-0698; E-mail: kbfnyf@aol.com





INTRODUCTION

Age-related macular degeneration (AMD) is one of the most common causes of severe, irreversible vision loss in older adults in developed countries. Neovascular AMD is characterized by abnormal growth of new blood vessels under or within the macula [1Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355: 1419-31.]. Vascular endothelial growth factor A (VEGF) is a key modulator of angiogenesis and promotes neovascularization in AMD [1Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355: 1419-31.-4Heier JS, Antoszyk AN, Pavan PR, et al. Ranibizumab for treatment of neovascular age-related macular degeneration a phase I/II multicenter, controlled, multidose study Ophthalmol 2006; 113: 633-42.]. Currently, several anti-VEGF drugs such as pegaptanib, ranibizumab and bevacizumab are used via the intravitreal route for treatment of neovascular AMD [5Jeganathan VSE, Verma N. Safety and efficacy of intravitreal anti-VEGF injections for age-related macular degeneration Curr Opin Ophthalmol 2009; 20: 223-5.].

Ranibizumab (Lucentis, Genentech, San Francisco, USA) is a recombinant humanized monoclonal G1K isotype antibody Fab with anti-angiogenetic VEGF A blocking properties [1Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355: 1419-31.-4Heier JS, Antoszyk AN, Pavan PR, et al. Ranibizumab for treatment of neovascular age-related macular degeneration a phase I/II multicenter, controlled, multidose study Ophthalmol 2006; 113: 633-42.]. The Food and Drug Administration (FDA) approved Ranibizumab since 2006 as an intravitreal injection treatment for neovascular AMD [1Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355: 1419-31.,5Jeganathan VSE, Verma N. Safety and efficacy of intravitreal anti-VEGF injections for age-related macular degeneration Curr Opin Ophthalmol 2009; 20: 223-5.]. Bevacizumab (Avastin, Genentech, San Francisco, USA) is a recombinant humanized full-length antibody that binds to all isoforms of VEGF. It was initially approved by the FDA for intravenous use against metastatic colorectal cancer, but is now commonly used off-label to treat a variety of retinal disorders including neovascular AMD, diabetic macular edema, and retinal vein occlusion [7Tseng JJ, Vance SK, Della Torre KE, et al. Sustained increased intraocular pressure related to intravitreal anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration J Glaucoma 2011. Epub].

Several adverse reactions after intravitreal injections of anti-VEGF treatment have been reported including subconjunctival hemorrhage [4Heier JS, Antoszyk AN, Pavan PR, et al. Ranibizumab for treatment of neovascular age-related macular degeneration a phase I/II multicenter, controlled, multidose study Ophthalmol 2006; 113: 633-42.-7Tseng JJ, Vance SK, Della Torre KE, et al. Sustained increased intraocular pressure related to intravitreal anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration J Glaucoma 2011. Epub], conjunctival hyperemia [4Heier JS, Antoszyk AN, Pavan PR, et al. Ranibizumab for treatment of neovascular age-related macular degeneration a phase I/II multicenter, controlled, multidose study Ophthalmol 2006; 113: 633-42.-7Tseng JJ, Vance SK, Della Torre KE, et al. Sustained increased intraocular pressure related to intravitreal anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration J Glaucoma 2011. Epub], transient and/or sustained elevated intraocular pressure (IOP) [1Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355: 1419-31.,4Heier JS, Antoszyk AN, Pavan PR, et al. Ranibizumab for treatment of neovascular age-related macular degeneration a phase I/II multicenter, controlled, multidose study Ophthalmol 2006; 113: 633-42.-9Jager RD, Aiello LP, Patel SC, et al. Risks of intravitreous injection: a comprehensive review Retina 2004; 24: 676-98.], anterior uveitis [1Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355: 1419-31.,8Ladas ID, Karagiannis DA, Rouvas AA, et al. Safety of repeat intravitreal injections of bevacizumab versus ranibizumab our experience after 2,000 injections Retina 2009; 29: 313-8.-10Pieramici DJ, Avery RL, Castellarin AA, et al. Case of anterior uveitis after intravitreal injection of bevacizumab Retina, J Retinal and Vitreous Diseases 2006; 26: 841-2.], iatrogenic cataract [1Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355: 1419-31.,5Jeganathan VSE, Verma N. Safety and efficacy of intravitreal anti-VEGF injections for age-related macular degeneration Curr Opin Ophthalmol 2009; 20: 223-5.], vitreous hemorrhage [1Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355: 1419-31.,4Heier JS, Antoszyk AN, Pavan PR, et al. Ranibizumab for treatment of neovascular age-related macular degeneration a phase I/II multicenter, controlled, multidose study Ophthalmol 2006; 113: 633-42.], retinal tear or detachment [1Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355: 1419-31.,4Heier JS, Antoszyk AN, Pavan PR, et al. Ranibizumab for treatment of neovascular age-related macular degeneration a phase I/II multicenter, controlled, multidose study Ophthalmol 2006; 113: 633-42.], central retinal vein occlusion [4Heier JS, Antoszyk AN, Pavan PR, et al. Ranibizumab for treatment of neovascular age-related macular degeneration a phase I/II multicenter, controlled, multidose study Ophthalmol 2006; 113: 633-42.] and endophthalmitis [1Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355: 1419-31.,4Heier JS, Antoszyk AN, Pavan PR, et al. Ranibizumab for treatment of neovascular age-related macular degeneration a phase I/II multicenter, controlled, multidose study Ophthalmol 2006; 113: 633-42.]. We report a case of a localized, subconjunctival, nodular inflammatory reaction at the site of multiple ranibizumab injections. Based on clinical appearance, anterior segment imaging and improvement with topical steroid treatment, we believe this lesion to be a pyogenic granuloma. To the best of our knowledge, this is the first case of pyogenic granuloma observed following intravitreal injections of anti-VEGF therapy.

CASE REPORT

An 87-year-old Caucasian man treated for neovascular AMD presented complaining of eye pain and redness one week after his last intravitreal ranibizumab injection in the right eye (Fig. 1a). The patient received OCT guided treatment with bevacizumab (0.125mg/0.05ml) starting in October 2005 prior to Federal Drug Administration (FDA) approval of ranibizumab for AMD treatment and received three bevacizumab (0.125mg/0.05ml) over an 8 month period of time. He elected to transition to a treat and extend protocol after FDA approval of ranibizumab for treatment of neovascular AMD and received twenty-one ranibizumab (0.5mg/0.05ml) injections without complications starting August 2006 and continued over a 48 month period time with his last injection on August 2010. All injections were administered 3.5-4mm posterior to the limbus in the inferotemporal quadrant varying one or two clock hours from previous injection sites using a 32 gauge needle following three drops of topical proparacaine (0.5%), two drops of ofloxacin (0.3%), and one drop of 5% povidone-iodine. According to the intravitreal injection protocol recommended in the literature, prior to each injection, the injection site was dried with a sterile cotton-tipped applicator. A wire lid speculum and non-sterile powder-free latex gloves were used for all injection procedures [11Aiello LP, Brucker AJ, Chang S, et al. Evolving guidelines for intravitreous injections Retina 2004; 24: S3-S19.].

Fig. (1)

(A) Color photograph shows the appearance of the right eye at presentation. There is hyperemia and edema of the inferotemporal bulbar conjunctiva. (B) Higher magnification of initial erythematous subconjunctival nodule at the site of prior intravitreal injection.



Fig. (2)

(A) Anterior slit lamp optical coherence tomography imaging showing a well-circumscribed nodule. (B) Ultrasound biomicroscopy showing no penetration of the normal sclera (black star).



Fig. (3)

Color photograph showing the appearance following 5 months topical steroid treatment. The conjunctival nodule has flattened leaving persistent dilated episcleral vessels and increased scleral translucency.



One week post intravitreal injection, the patient had stable corrected visual acuity of 20/200 in the affected right eye. There was localized, inferotemporal hyperemia of the bulbar conjunctiva at the site of the injection. Within the area of hyperemia there was an elevated, subconjunctival erythematous nodule, which was slightly mobile when depressed with a cotton tip applicator (Fig. 1b). There was no evidence of perilimbal vessel injection. On eyelid eversion, there was no tarsal or forniceal conjunctival involvement or foreign body. Anterior exam revealed trace cells and 1+ flare reaction in the anterior chamber. No hypopyon or vitreous cells were noted. Lens, optic nerve and peripheral retinal exam were unremarkable. The left eye was unremarkable and showed no evidence of inflammation.

Slit lamp optical coherence tomography (SL-OCT) (Fig. 2a) and ultrasound biomicroscopy (UBM) (Fig. 2b) revealed a well-circumscribed, solid lesion without scleral penetration. The patient was started on ofloxacin (0.3%) and rimexolone (1%) four times per day in the right eye. Two weeks post-injection, the patient self-discontinued the ofloxacin drops and was using only rimexolone twice daily. While the nodule persisted and conjunctival hyperemia had improved minimally, the patient reported little discomfort. He was transitioned to prednisolone acetate (1%) four times per day and fluorometholone ointment (0.1%) at bedtime. The lesion decreased in size slowly over five months and prednisolone acetate was slowly tapered to one drop daily. The hyperemia resolved and there was trace hyperpigmentation over the area of minimal subconjunctival elevation (Fig. 3). Surgical excision and biopsy was deferred due to improvement with the topical steroid. The patient’s AMD treatment was changed to pro re nata (PRN) optical coherence tomography guided dosing and has not since required or received any further injections. If clinically indicated, another injection site will be considered to prevent further complications.

DISCUSSION

Safety profiles are closely monitored in the original clinical trials of a medication, but long term use of a medication can subsequently lead to the new presentation of adverse events or drug reactions [2Chen Y, Wiesmann C, Fuh G, et al. Selection and analysis of an optimized anti-vegf antibody: crystal structure of an affinity-matured fab in complex with antigen J Mol Bio 1999; 293: 865-1.]. The most common ocular adverse events for patients receiving ranibizumab in randomized clinical trials were transient subconjunctival hemorrhage [4Heier JS, Antoszyk AN, Pavan PR, et al. Ranibizumab for treatment of neovascular age-related macular degeneration a phase I/II multicenter, controlled, multidose study Ophthalmol 2006; 113: 633-42.-7Tseng JJ, Vance SK, Della Torre KE, et al. Sustained increased intraocular pressure related to intravitreal anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration J Glaucoma 2011. Epub], intraocular inflammation [1Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355: 1419-31.,8Ladas ID, Karagiannis DA, Rouvas AA, et al. Safety of repeat intravitreal injections of bevacizumab versus ranibizumab our experience after 2,000 injections Retina 2009; 29: 313-8.-10Pieramici DJ, Avery RL, Castellarin AA, et al. Case of anterior uveitis after intravitreal injection of bevacizumab Retina, J Retinal and Vitreous Diseases 2006; 26: 841-2.] and transient and/or sustained elevated intraocular pressure (IOP) [1Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355: 1419-31.,4Heier JS, Antoszyk AN, Pavan PR, et al. Ranibizumab for treatment of neovascular age-related macular degeneration a phase I/II multicenter, controlled, multidose study Ophthalmol 2006; 113: 633-42.-9Jager RD, Aiello LP, Patel SC, et al. Risks of intravitreous injection: a comprehensive review Retina 2004; 24: 676-98.]. In one prospective study monitoring for transient post injection IOP elevations after ranibizumab injections, the authors noted that mild injection site reactions such as subconjunctival hemorrhage and /or hyperemia were common (59.2%) [6Gismondi M, Salati C, Salvetat ML, et al. Short-term effect of intravitreal injection of ranibizumab (lucentis) on intraocular pressure J Glaucoma 2009; 18: 658-1.].

Transient ischemia of the ocular surface after intravitreal bevacizumab has been reported with nonperfusion of conjunctival, episcleral and scleral vessels around the injection site. This ischemia, hypothesized to be inflammatory in nature, was treated with topical steroids and resolved over three weeks [12Georgakarakos ND, Sullivan P, Dowler J. Injection site ischemia and inflammation after intravitreal bevacizumab Retin Cases Brief Rep 2010; 4: 294-6.]. Our case did not show any signs of nonperfusion; rather, hyperemia of the blood vessels overlying the injection site was seen.

Intravitreal ranibizumab injections have rarely been associated with noninfectious anterior uveitis [1Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355: 1419-31.,8Ladas ID, Karagiannis DA, Rouvas AA, et al. Safety of repeat intravitreal injections of bevacizumab versus ranibizumab our experience after 2,000 injections Retina 2009; 29: 313-8.-10Pieramici DJ, Avery RL, Castellarin AA, et al. Case of anterior uveitis after intravitreal injection of bevacizumab Retina, J Retinal and Vitreous Diseases 2006; 26: 841-2.]. Within one week after injection, our patient developed active anterior inflammation and a localized inflammatory reaction at the site of intravitreal injection. He had previously tolerated multiple bevacizumab and ranibizumab treatments without evidence of post-injection inflammation.

The differential diagnosis at presentation included foreign body reaction, scleral abscess, nodular scleritis, and pyogenic granuloma. Anterior imaging with SL-OCT and UBM revealed a solid nodule that did not involve the sclera, which was consistent with a localized reaction. We believe this reaction occurred as a result of inflammatory materials deposited in the process of injection, creating a pyogenic granuloma reaction and secondary anterior chamber inflammation.

Pyogenic granulomas are red colored tumors that appear on the palpebral or bulbar conjunctiva in areas of vascularized tissue submitted to chronic inflammatory injury [13D'Hermies F, Meyer A, Morel X, et al. Conjunctiva pyogenic granuloma in a patient with chalazions French J Ophthalmol 2003; 26: 1085-8.-19Venkatesh P, Lakshmaiah NC, Chawla R. Insect wing conjunctival granuloma Cornea 2003; 22: 489-90.]. Histopathologically, they contain granulation tissue with blood vessels arranged in a fan-shaped configuration and have an associated acute and chronic inflammatory cell infiltrate in a loose connective tissue stroma [15Grossniklaus H, Green WR, Luckenbach M, Chan CC. Conjunctival Lesions in adults. a clinical and histopathologic review Cornea 1987; 6: 78-116.,16Ferry AP. Pyogenic granulomas of the eye and ocular adnexa: a study of 100 cases Trans Am Ophthalmol Soci 1989; 87: 327-43.]. Although often associated with trauma [14Damasceno EF, Pereira C, Damasceno NAP, et al. Pyogenic granuloma after retinal detachment surgery with scleral buckle: case report Arq Bras Oftalmol 2009; 72: 543-4.-16Ferry AP. Pyogenic granulomas of the eye and ocular adnexa: a study of 100 cases Trans Am Ophthalmol Soci 1989; 87: 327-43.], surgery [14Damasceno EF, Pereira C, Damasceno NAP, et al. Pyogenic granuloma after retinal detachment surgery with scleral buckle: case report Arq Bras Oftalmol 2009; 72: 543-4.-17Googe JM, Mackman G, Peterson MR. Pyogenic granulomas of the cornea Survey Ophthalmol 1984; 29: 188-92.] and chalazions [13D'Hermies F, Meyer A, Morel X, et al. Conjunctiva pyogenic granuloma in a patient with chalazions French J Ophthalmol 2003; 26: 1085-8.-16Ferry AP. Pyogenic granulomas of the eye and ocular adnexa: a study of 100 cases Trans Am Ophthalmol Soci 1989; 87: 327-43.], there are reports of pyogenic granuloma formation after foreign bodies such as natural or synthetic fibers [16Ferry AP. Pyogenic granulomas of the eye and ocular adnexa: a study of 100 cases Trans Am Ophthalmol Soci 1989; 87: 327-43.], contact lens [16Ferry AP. Pyogenic granulomas of the eye and ocular adnexa: a study of 100 cases Trans Am Ophthalmol Soci 1989; 87: 327-43.], scleral buckle [14Damasceno EF, Pereira C, Damasceno NAP, et al. Pyogenic granuloma after retinal detachment surgery with scleral buckle: case report Arq Bras Oftalmol 2009; 72: 543-4.], and insect wing [14Damasceno EF, Pereira C, Damasceno NAP, et al. Pyogenic granuloma after retinal detachment surgery with scleral buckle: case report Arq Bras Oftalmol 2009; 72: 543-4.]. We hypothesize that a component of the intravitreal injection procedure such as talc from a disposable glove, cotton fibers from the sterile applicator, or silicone oil derived from the syringe [20Freund KB, Laud K, Eandi CM, Spaide RF. Silicone oil droplets following intravitreal injection Retina 2006; 26: 701-3.-22Kocabora MS, Ozbilen KT, Serefoglu K. Intravitreal silicone oil droplets following pegaptanib injection Acta Ophthalmol 2010; 88: e44-5.] could have triggered foreign body reaction at the level of the conjunctiva. Also, repeated injections in the same quadrant of the eye might have increased the risk of this complication.

Intravitreal anti-VEGF agents including ranibizumab and bevacizumab are a safe and effective treatment for neovascular AMD [5Jeganathan VSE, Verma N. Safety and efficacy of intravitreal anti-VEGF injections for age-related macular degeneration Curr Opin Ophthalmol 2009; 20: 223-5.]. Even with the evidence and safety profiles available from the original clinical trials, new presentations of adverse events may occur as the usage of intravitreal anti-VEGF therapy continues to grow. The safety data on these treatment modalities will need to be continuously monitored and the potential risks and benefits of intravitreal anti-VEGF agents should be discussed with patients receiving treatment for neovascular AMD [9Jager RD, Aiello LP, Patel SC, et al. Risks of intravitreous injection: a comprehensive review Retina 2004; 24: 676-98.].

CONFLICTS OF INTEREST

Financial support from the LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Institute, and The Macula Foundation Inc. The funding organizations had no role in the design or conduct of this research.

Financial disclosure includes Genentech (Consultant, Research Support-KBF), Alcon (Consultant-KBF) and Alimera (Consultant-KBF).

REFERENCES

[1] Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355: 1419-31.
[2] Chen Y, Wiesmann C, Fuh G, et al. Selection and analysis of an optimized anti-vegf antibody: crystal structure of an affinity-matured fab in complex with antigen J Mol Bio 1999; 293: 865-1.
[3] Dafer RM, Schneck M. Intravitreal ranibizumab and bevacizumab: a review of risk Semin Ophthalmol 2007; 22: 201-4.
[4] Heier JS, Antoszyk AN, Pavan PR, et al. Ranibizumab for treatment of neovascular age-related macular degeneration a phase I/II multicenter, controlled, multidose study Ophthalmol 2006; 113: 633-42.
[5] Jeganathan VSE, Verma N. Safety and efficacy of intravitreal anti-VEGF injections for age-related macular degeneration Curr Opin Ophthalmol 2009; 20: 223-5.
[6] Gismondi M, Salati C, Salvetat ML, et al. Short-term effect of intravitreal injection of ranibizumab (lucentis) on intraocular pressure J Glaucoma 2009; 18: 658-1.
[7] Tseng JJ, Vance SK, Della Torre KE, et al. Sustained increased intraocular pressure related to intravitreal anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration J Glaucoma 2011. Epub
[8] Ladas ID, Karagiannis DA, Rouvas AA, et al. Safety of repeat intravitreal injections of bevacizumab versus ranibizumab our experience after 2,000 injections Retina 2009; 29: 313-8.
[9] Jager RD, Aiello LP, Patel SC, et al. Risks of intravitreous injection: a comprehensive review Retina 2004; 24: 676-98.
[10] Pieramici DJ, Avery RL, Castellarin AA, et al. Case of anterior uveitis after intravitreal injection of bevacizumab Retina, J Retinal and Vitreous Diseases 2006; 26: 841-2.
[11] Aiello LP, Brucker AJ, Chang S, et al. Evolving guidelines for intravitreous injections Retina 2004; 24: S3-S19.
[12] Georgakarakos ND, Sullivan P, Dowler J. Injection site ischemia and inflammation after intravitreal bevacizumab Retin Cases Brief Rep 2010; 4: 294-6.
[13] D'Hermies F, Meyer A, Morel X, et al. Conjunctiva pyogenic granuloma in a patient with chalazions French J Ophthalmol 2003; 26: 1085-8.
[14] Damasceno EF, Pereira C, Damasceno NAP, et al. Pyogenic granuloma after retinal detachment surgery with scleral buckle: case report Arq Bras Oftalmol 2009; 72: 543-4.
[15] Grossniklaus H, Green WR, Luckenbach M, Chan CC. Conjunctival Lesions in adults. a clinical and histopathologic review Cornea 1987; 6: 78-116.
[16] Ferry AP. Pyogenic granulomas of the eye and ocular adnexa: a study of 100 cases Trans Am Ophthalmol Soci 1989; 87: 327-43.
[17] Googe JM, Mackman G, Peterson MR. Pyogenic granulomas of the cornea Survey Ophthalmol 1984; 29: 188-92.
[18] Horton JC, Mathers WD, Zimmerman LE. Pyogenic Granuloma of the palpebral conjunctiva associated with contact lens wear Cornea 1990; 9: 359-61.
[19] Venkatesh P, Lakshmaiah NC, Chawla R. Insect wing conjunctival granuloma Cornea 2003; 22: 489-90.
[20] Freund KB, Laud K, Eandi CM, Spaide RF. Silicone oil droplets following intravitreal injection Retina 2006; 26: 701-3.
[21] Bakri SJ, Ekdawi NS. Intravitreal silicone oil droplets after intravitreal drug injections Retina 2008; 28: 996-1001.
[22] Kocabora MS, Ozbilen KT, Serefoglu K. Intravitreal silicone oil droplets following pegaptanib injection Acta Ophthalmol 2010; 88: e44-5.
Track Your Manuscript:


Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


Browse Contents




Webmaster Contact: info@benthamopen.net
Copyright © 2020 Bentham Open