rheumatoid arthritis ( ra ) and other connective tissue disorders are frequently associated with certain types of corneal or / and scleral pathology such as peripheral ulcerative keratitis , dry eye syndrome , and scleritis .
it is also known that these conditions may lead to perforation of the eye by compromising the integrity of its outermost layers .
keratoconus ( kc ) is generally regarded as an isolated condition with no apparent ophthalmic or systemic associations at the time of diagnosis . however , elevated levels of corneal proinflammatory cytokines such as interleukin ( il)-1 have been linked to corneal thinning , implying the involvement of the immune system in the pathogenesis of kc . only a small number of autoimmune diseases ( e.g. , ra , asthma , inflammatory bowel disease ) have been related to kc , while others have not ( e.g. , systemic lupus , crohn s disease , myasthenia gravis , and multiple sclerosis ) .
cell - mediated mechanisms are suggested to play a pivotal role in the pathogenesis of ectatic corneal disorders and kc itself .
further , confocal microscopy has revealed that in patients with ra , the central corneal and stromal thicknesses are significantly lower compared with controls , and these patients have significantly higher numbers of hyperreflective stromal cells .
the activation of these keratocytes is mediated by proinflammatory cytokines , such as il-1 and il-6 .
we report a case of paracentral corneal perforation in a patient with keratoconus and a previously undiagnosed connective tissue disorder .
a 53-year - old man presented in the emergency room complaining of severe ocular pain with sudden onset and a significant decrease in visual acuity in his left eye .
regarding his ocular history , the patient noted that his ophthalmologist had been modifying his spectacle prescription annually over the last 13  years because of the increasing myopic shift .
the patient reported no systemic drug intake except for analgesics for constant lumbar back pain .
the patient s best corrected visual acuity was measured cf at 10  cm for the left and 20/60 for his right eye .
his spectacle prescription at the time of the examination was : 1.00/5.5    100 os and 4.5/4.5    70 od .
slit lamp biomicroscopy revealed a paracentral corneal perforation , 1    2  mm , accompanied by iris prolapse , corneal thinning , and a markedly shallow anterior chamber in the left eye .
the right eye displayed clinical features of moderate keratoconus , which was confirmed by corneal topography ( magellan mapper , nidek ; figs .  1 and 2).fig . 
steep corneal curvature on biomicroscopy raised suspicions of a coexistent keratoconus topography image demonstrating significant keratoconus on the right eye the patient was immediately prepared for surgical intervention in order to preserve the integrity of the affected eye .
amniotic membrane ( am ) was primarily available and transplanted in an attempt to seal the perforation and promote corneal healing ( fig . 
cryopreserved am was attached over the perforation in multiple layers and covered with an epithelial - side - up , limbal - sutured sheet .
the surgical technique involved scraping of residual corneal epithelium and 360 limbal peritomy of the conjunctiva prior to am transplantation .
the outermost of the multiple layers was sutured with 8/0 vicryl on the cornea whereas the overlaid transplant was sutured at the limbus with a running 10/0 nylon .
a bandage contact lens was applied at the end of the operation in order to promote reepithelialization of am and to prevent mechanical rubbing of the transplant on blinking.fig . 
3photo of left eye on second post - op day after amniotic membrane transplantation in multiple layers in an attempt to maintain the eye s anatomical integrity photo of left eye on second post - op day after amniotic membrane transplantation in multiple layers in an attempt to maintain the eye s anatomical integrity further blood tests revealed a significantly elevated rheumatoid factor at 2,170  iu / ml ( reference value < 20  iu / ml ) .
specific blood tests in addition to detailed clinical examination carried out by an orthopedic surgeon and immunologist confirmed the diagnosis of ra , and the patient was referred to rheumatologists for further assessment .
the operated on eye displayed a well - formed anterior chamber , without any leakage , over the 3 post - op weeks .
visual acuity was slightly improved to cf at 50  cm . however , reepithelialization failed to cover am completely whilst subsequent tissue thinning resulted in re - leakage at week  4 postoperatively .
one month after corneal grafting and while on systemic immunosuppressants , the patient developed endophthalmitis with unfavorable outcome .
kc is a noninflammatory corneal disorder in which stromal thinning and ectasia result in an atypical corneal shape .
although the etiology is not completely understood , there is evidence suggesting that kc probably represents a multifactorial process .
kc with acute hydrops can be complicated with spontaneous corneal perforation ; however , this has been reported mainly in cases with advanced kc .
nevertheless , spontaneous perforation in mild to moderate kc cases has also been reported recently . ophthalmic involvement in autoimmune disorders such as ra , systemic lupus erythematosus , and
sjgren syndrome has been extensively described . however , many patients experience ocular sequelae during the course of undiagnosed immunological disorders
. reduced tear secretion , chronic inflammation of the ocular surface , as well as ultrastructural abnormalities are believed to play a major part in decompensating the ocular surface .
this condition may lead to spontaneous perforation in sporadic cases . in our case , am transplantation was used as a first - line solution since previous studies showed that urgent penetrating keratoplasties in perforated eyes displayed higher rates of graft failure compared to those performed several weeks to months following the perforation [ 10 , 11 ] .
multilayer am transplantation has been reported to promote epithelial healing and reduce inflammation , neovascularization , and scarring in a diversity of external eye disorders .
am - related local anti - inflammatory effects contribute to faster and more efficient reepithelialization .
furthermore , am serves as a biological scaffolding in cases where normal tissue is lost and promotes reinforcement or even sealing of small perforations . am has been used in patients with ra - related epithelial defects as a temporizing solution with the aim for delayed reconstruction . however , as solomon and colleagues reported , am transplantation showed poorer outcomes in patients with systemically undertreated ra compared to other autoimmune conditions like ocular pemphigoid or even sjogren s .
other authors have proposed cyanoacrylate and fibrin glue adhesives as an efficacious solution in cases where corneal perforations occur [ 13 , 14 ] . in our case , am transplantation was preferred over other treatment modalities mainly due to severe inflammation of the ocular surface and the small size of the perforation . besides , the diagnosis of ra had not yet been established .
furthermore , penetrating keratoplasty does not represent a first - choice operation in our country due to the relatively restricted number of centers authorized to perform corneal transplantations and to limited availability of corneal grafts . in our patient , although the am transplant initially provided a sufficient corneal sealing , it failed as a long - term solution due to poor reepithelialization and the progressive tissue degradation .
recurrent aqueous humor leak necessitated an emergent penetrating keratoplasty , which took place in another center .
there are quite a few studies that extensively describe the relationship between ra and ocular surface disorders that may permanently affect vision [ 15 , 16 ] .
kc is another thoroughly studied condition that , apart from major refractive alterations , may occasionally cause corneal perforation when undiagnosed or / and untreated .
to the best of our knowledge , this is the first report of a case with corneal perforation arising from coexistent kc and ra .
it seems possible that the impact of these conditions is more severe when they interact .
we should therefore raise awareness and either rule out or efficiently treat underlying connective tissue disorders in patients with kc .
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 purposethe purpose of this study is to report a case of corneal perforation in a patient with undiagnosed keratoconus and underlying rheumatoid arthritis.methodsthis is a retrospective case study based on the patient s medical records and followed by a brief review of the literature.resultsa 53-year - old patient was referred to our department for acute pain and sudden decrease of visual acuity in his left eye . 
 corneal perforation was detected and attributed to a previously undiagnosed and untreated keratoconus . 
 additional laboratory work - up and clinical examination revealed a coexisting rheumatoid arthritis . 
 amniotic membrane was originally transplanted in order to maintain the structural integrity and promote healing of the perforated eye . 
 subsequently , the patient underwent a penetrating keratoplasty , though with unfavorable results due to postoperative endophthalmitis.conclusionsrheumatoid arthritis may be associated with higher risk of corneal perforation in patients with ectatic degenerative diseases such as keratoconus . 
Introduction
Case report
Discussion
Conclusion
Conflict of interest
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