cryptogenic organizing pneumonia ( cop ) , also known as bronchiolitis obliterans organizing pneumonia ( boop ) , is a relatively rare disorder with distinctive clinical , imaging and pathological features .
the pathological findings are characterized by plugs of granulation tissue lying within small airways , alveolar ducts and alveoli and by chronic inflammatory cell infiltration in the alveolar walls .
cop is defined as idiopathic and any cause for the development of pneumonia such as infection or underlying tissue disease is excluded .
patients with cop manifest rapid clinical and imaging improvement with corticosteroid therapy , but suffer from frequent relapses . through histopathological examination and clinical observation , uveitis is usually classified into two categories , granulomatous and nongranulomatous .
hypopyon is the accumulation of white blood cells in the anterior chamber and is often observed in nongranulomatous uveitis .
nongranulomatous presentations are mostly idiopathic or due to hla - b27 antigen involvement [ 2 , 3 , 4 ] . it is well known that systemic diseases that can be associated with nongranulomatous uveitis include behet 's disease , ankylosing spondylitis , inflammatory bowel disease and psoriasis . although the cause is not fully disclosed , certain ocular and systemic conditions might be the underlying association with nongranulomatous uveitis . in this report
, we describe two cases of cop who developed bilateral anterior uveitis with hypopyon unresponsive to topical corticosteroid therapy but responsive to systemic corticosteroid therapy . in addition , the clinical condition of their cop was concomitant to that of their intraocular inflammation .
a 65-year - old woman was referred for evaluation of bilateral decreased vision and glaucoma .
she had undergone a series of treatment for breast cancer with surgery , radiation and chemotherapy 14 years earlier .
concerning her ocular history , she had been diagnosed as having an epiretinal macular membrane on her right eye and received a vitrectomy and phacoemulsification 3 years prior .
the intraocular inflammation was resistant to topical betamethasone administration but decreased spontaneously in 1 year . despite the uveitis
being mostly controlled , the intraocular pressure in both eyes had gradually increased and she was referred to our hospital .
the initial ophthalmic examination disclosed a best - corrected visual acuity ( bcva ) of 20/50 in the right eye and 20/80 in the left eye .
the intraocular pressure was 25 mm hg in the right and 40 mm hg in the left eye .
slit - lamp examination demonstrated no sign of uveitis or retinal disease besides pseudophakia in the right eye and a cataract in the left eye .
the results of the laboratory investigations of serum including angiotensin - converting enzyme , antinuclear antibodies , rheumatoid factor and antineutrophil cytoplasmic antibodies were unremarkable despite for the presence of elevated c - reactive protein .
serological analyses indicated that there was no active infection of syphilis , human t - cell lymphoma virus 1 , herpes simplex virus or varicella zoster virus .
the results of human leukocyte antigen type b testing were positive for b-60 and b-61 .
after admission , the patient underwent phacoemulsification surgery with intraocular lens implantation and a viscocanalostomy in the left eye for her cataract and glaucoma .
her bcva improved to 20/40 in the right eye and 20/32 in the left eye , and both the intraocular inflammation and intraocular pressure were controlled .
five months later , the cellular infiltration with hypopyon in the anterior chamber was seen in both eyes ( fig .
then , the patient received systemic prednisolone ( psl ) 40 mg / day administered orally to treat the aggravated cop , and both lung symptoms and intraocular inflammation diminished .
when psl dosage was reduced to 5 mg / day during tapering , cellular infiltration in the anterior chamber and hypopyon relapsed and bcva of her eyes , particularly of her left eye , declined despite administration of topical dexamethasone .
an optical coherence tomography ( oct ) examination showed a macular edema in her left eye ( fig .
although a subconjunctival triamcinolone injection was given when her left bcva reached 20/200 , there was little improvement .
then , oral psl was increased to 30 mg / day , and the intraocular inflammation subsequently decreased and her bcva gradually recovered ( fig .
, yttrium - aluminum - argon ( yag ) laser treatment was performed to treat posterior capsule opacification in her left eye . during the clinical course
, there was temporal intraocular pressure elevation , which could be maintained by topical antiglaucoma medication . at the middle of the relapse period ,
cytological examination of infiltrated cells in the anterior chamber showed neutrophils and a few lymphocytes , but no atypical cell .
the genomic dna in aqueous humor was analyzed to screen infectious pathogens including bacteria , parasites , and viruses by comprehensive polymerase chain reaction .
, there were no physical findings of skin disease , oral aphtha , pudendal ulcers , joint inflammation , spondylitis or digestive symptoms . a 69-year - old woman presented with blurred vision in both eyes .
her ocular history expressed age - related macular degeneration in both eyes 6 years prior .
subsequently , she was referred to our hospital . the initial ophthalmic examination disclosed a bcva of 20/25 in the right eye and 20/20 in the left eye .
slit - lamp examination demonstrated bilateral fine keratic precipitates , hypopyon and intensive cell infiltration in the anterior chamber .
there was a mild cataract but no sign of posterior uveitis or diabetic change in the retina .
3 . the results of the laboratory investigations of serum including angiotensin - converting enzyme , antinuclear antibodies , rheumatoid factor , and antineutrophil cytoplasmic antibodies were unremarkable despite for the presence of elevated c - reactive protein and hba1c ( 7.1% ) .
serological analyses showed no active infection of syphilis , human t - cell lymphoma virus 1 , herpes simplex virus or varicella zoster virus .
the results of human leukocyte antigens type b testing were positive for b-51 and b-61 .
one month later , she was administered systemic psl 40 mg / day orally to treat cop . the intraocular cell infiltration and hypopyon diminished in 1 month . during psl
an oct examination showed an epiretinal membrane and macular edema in both eyes ( fig .
the psl administration was reduced gradually and then halted , with no recurrence of uveitis .
therefore , the cytological examination of infiltrated cells in the anterior chamber or the genomic dna analysis of infectious pathogens was not performed . during observation
, there were no physical findings of skin disease , oral aphtha , pudendal ulcers , joint inflammation , spondylitis or digestive symptoms .
a 65-year - old woman was referred for evaluation of bilateral decreased vision and glaucoma .
she had undergone a series of treatment for breast cancer with surgery , radiation and chemotherapy 14 years earlier .
concerning her ocular history , she had been diagnosed as having an epiretinal macular membrane on her right eye and received a vitrectomy and phacoemulsification 3 years prior .
the intraocular inflammation was resistant to topical betamethasone administration but decreased spontaneously in 1 year . despite the uveitis
being mostly controlled , the intraocular pressure in both eyes had gradually increased and she was referred to our hospital .
the initial ophthalmic examination disclosed a best - corrected visual acuity ( bcva ) of 20/50 in the right eye and 20/80 in the left eye .
the intraocular pressure was 25 mm hg in the right and 40 mm hg in the left eye .
slit - lamp examination demonstrated no sign of uveitis or retinal disease besides pseudophakia in the right eye and a cataract in the left eye .
the results of the laboratory investigations of serum including angiotensin - converting enzyme , antinuclear antibodies , rheumatoid factor and antineutrophil cytoplasmic antibodies were unremarkable despite for the presence of elevated c - reactive protein .
serological analyses indicated that there was no active infection of syphilis , human t - cell lymphoma virus 1 , herpes simplex virus or varicella zoster virus .
the results of human leukocyte antigen type b testing were positive for b-60 and b-61 .
after admission , the patient underwent phacoemulsification surgery with intraocular lens implantation and a viscocanalostomy in the left eye for her cataract and glaucoma .
her bcva improved to 20/40 in the right eye and 20/32 in the left eye , and both the intraocular inflammation and intraocular pressure were controlled .
five months later , the cellular infiltration with hypopyon in the anterior chamber was seen in both eyes ( fig .
then , the patient received systemic prednisolone ( psl ) 40 mg / day administered orally to treat the aggravated cop , and both lung symptoms and intraocular inflammation diminished .
when psl dosage was reduced to 5 mg / day during tapering , cellular infiltration in the anterior chamber and hypopyon relapsed and bcva of her eyes , particularly of her left eye , declined despite administration of topical dexamethasone .
an optical coherence tomography ( oct ) examination showed a macular edema in her left eye ( fig .
although a subconjunctival triamcinolone injection was given when her left bcva reached 20/200 , there was little improvement .
then , oral psl was increased to 30 mg / day , and the intraocular inflammation subsequently decreased and her bcva gradually recovered ( fig .
, yttrium - aluminum - argon ( yag ) laser treatment was performed to treat posterior capsule opacification in her left eye . during the clinical course
, there was temporal intraocular pressure elevation , which could be maintained by topical antiglaucoma medication . at the middle of the relapse period ,
cytological examination of infiltrated cells in the anterior chamber showed neutrophils and a few lymphocytes , but no atypical cell .
the genomic dna in aqueous humor was analyzed to screen infectious pathogens including bacteria , parasites , and viruses by comprehensive polymerase chain reaction .
, there were no physical findings of skin disease , oral aphtha , pudendal ulcers , joint inflammation , spondylitis or digestive symptoms .
she had undergone treatment for ovarian cancer with surgery 8 years earlier . in addition , she had been regularly examined and treated for cop and nephrolithiasis . her ocular history expressed age - related macular degeneration in both eyes 6 years prior .
the initial ophthalmic examination disclosed a bcva of 20/25 in the right eye and 20/20 in the left eye .
slit - lamp examination demonstrated bilateral fine keratic precipitates , hypopyon and intensive cell infiltration in the anterior chamber .
there was a mild cataract but no sign of posterior uveitis or diabetic change in the retina .
3 . the results of the laboratory investigations of serum including angiotensin - converting enzyme , antinuclear antibodies , rheumatoid factor , and antineutrophil cytoplasmic antibodies were unremarkable despite for the presence of elevated c - reactive protein and hba1c ( 7.1% ) .
serological analyses showed no active infection of syphilis , human t - cell lymphoma virus 1 , herpes simplex virus or varicella zoster virus .
the results of human leukocyte antigens type b testing were positive for b-51 and b-61 .
one month later , she was administered systemic psl 40 mg / day orally to treat cop . the intraocular cell infiltration and hypopyon diminished in 1 month . during psl
an oct examination showed an epiretinal membrane and macular edema in both eyes ( fig .
the psl administration was reduced gradually and then halted , with no recurrence of uveitis .
therefore , the cytological examination of infiltrated cells in the anterior chamber or the genomic dna analysis of infectious pathogens was not performed . during observation
, there were no physical findings of skin disease , oral aphtha , pudendal ulcers , joint inflammation , spondylitis or digestive symptoms .
in the present study , we described two cases that had common points in their phenotype . first , both cases showed bilateral anterior uveitis with hypopyon .
their intraocular inflammation was unresponsive to the administration of topical corticosteroids but showed a greater response to systemic corticosteroid administration ( sca ) .
furthermore , both patients were receiving treatments for cop , and had medical histories of malignant tumors .
however , neither was identified with any systemic disease that could be associated with uveitis .
nongranulomatous uveitis is characterized by fine keratic precipitates , and in severe cases , fibrinous clotting or hypopyon in the anterior chamber .
the most common form of nongranulomatous anterior uveitis is acute anterior uveitis , which is associated with the hla - b27 allele [ 2 , 3 , 5 ] .
the ocular feature of hla - b27-associated acute anterior uveitis is acute onset of unilateral inflammation , and is common in males between the ages of 2040 years . in this series , both cases were hla - b27 negative , and the uveitis was bilateral .
other diseases that could be associated with uveitis were screened . by the absence of systemic symptoms such as skin lesion , genital ulcer , oral aphtha and digestive symptoms ,
the laboratory investigations also eliminated the involvement of ankylosing spondylitis , arthritis , inflammatory bowel disease , sarcoidosis and infection .
in addition , several drugs including cidofovir and rifabutin are reported to induce uveitis . in the present study
, neither patient had taken those medicines during the period in which they contracted uveitis .
it is also known that the malignant neoplasm can introduce hypopyon that resembles intraocular inflammation [ 7 , 8 , 9 ] .
since they had not shown any recurrence for several years , it was assumed that their malignancies were controlled .
additionally , the cytological analysis of aqueous humor with cell infiltration in case 1 showed a moderate inflammation pattern without neoplastic cell . through the follow - up period of ovarian cancer without anticancer therapy in case 2
, there was no sign of recurrent cancer or metastasis . from these facts , it is unlikely that their malignancy is associated with uveitis in their eyes .
cop is diagnosed by its typical pathological findings of organizing pneumonia and the absence of any identified cause .
the organizing pneumonia occurs in cases of autoimmune diseases such as rheumatoid arthritis and sjgren 's syndrome .
several reports have described how cop accompanies uveitis as a part of behet 's disease [ 12 , 13 ] . in those cases ,
although the uveitis in our report developed concomitant to cop , there was no clinical indication to suggest a diagnosis of behet 's disease . additionally , the anterior uveitis in our patients was resistant to topical corticosteroid drops , which rarely occurs during anterior uveitis care .
this suggests that anterior uveitis in our cases was associated with cop . at present , there is one report that describes the complications of cop and uveitis without any cause . in this case ,
bilateral nongranulomatous uveitis was unresponsive to topical corticosteroid treatment , but systemic corticosteroid treatment had a more positive effect .
the present findings suggest the possibility that there is a novel cause of uveitis that shares the same etiology with cop .
further investigation with increased numbers of case studies and statistical analysis may result in the discovery of new symptoms for uveitis and cop .
 two female patients with histories of cancer who showed cryptogenic organizing pneumonia ( cop ) complications and bilateral anterior uveitis with hypopyon were examined . 
 both patients had suffered from cop and received intermitted systemic corticosteroid administration ( sca ) . the first patient , a 65-year - old woman with a history of breast cancer , showed bilateral uveitis with hypopyon . 
 the topical corticosteroid treatment was ineffective . 
 after sca for the treatment of cop was started , the hypopyon gradually dissipated . upon termination of sca 
 , uveitis relapses were controlled by renewed sca . 
 the other patient , a 69-year - old woman with a history of ovarian cancer , showed bilateral anterior uveitis with hypopyon . 
 her intraocular outcome did not improve by the topical corticosteroid administration , but sca that was applied to treat cop led to remission of uveitis . 
 imaging examinations , biochemical analysis , symptoms or hla - b27 antigen screenings in either patient did not explain the development of uveitis . 
 bilateral anterior uveitis is commonly related to autoimmune disease or systemic syndrome . 
 we report two cases with cop that developed bilateral anterior uveitis with hypopyon resistant to topical administration but responsive to systemic administration of corticosteroid . 
 these findings suggest that cop can be associated with the etiology of anterior uveitis . 