Resident Perspectives

Abstract

Prospective study on aflibercept to treat PEDs secondary to nAMDAge-related macular degeneration (AMD) is one of the leading causes of blindness. Pigment epithelial detachments (PED) can accompany neovascular AMD (nAMD) in as many as 62% of patients.1Coscas F. Coscas G. Souied E. Tick S. Soubrane G. Optical coherence tomography identification of occult choroidal neovascularization in age-related macular degeneration.Am J Ophthalmol. 2007; 144: 529-599Google Scholar PEDs are thought to be formed by the accumulation of fluid, blood, drusenoid material or fibrovascular tissue, which separates the retinal pigment epithelium from Bruch's membrane.2Pepple K. Mruthyunjaya P. Retinal pigment epithelial detachments in age-related macular degeneration: classification and therapeutic options.Semin Ophthalmol. 2011; 26 (5. Holz FG, Pauleikhoff D, Klein R, Bird AC): 198-208Crossref PubMed Scopus (34) Google Scholar Anti-VEGF treatment has become the mainstay of treatment for neovascular AMD. However, there is a paucity in the literature on the effects of aflibercept on PEDs secondary to nAMD. In this issue, Diaconita et al. (2019) report on their prospective, exploratory, open-label study aimed at understanding the effects of intravitreal aflibercept in treating patients with PED secondary to nAMD.3Diconita V. Li B. Pal L. Bahnacy F. Gonder J.R. Prospective evaluation of aflibercept in the treatment of pigment epithelial detachments secondary to neovascular age related macular degeneration.Can J Ophthalmol. 2019; 54: 626-634Google ScholarThe authors recruited 36 patients (37 eyes) who were ≥55 years of age with PEDs secondary to nAMD and no previous anti-VEGF injections. Patients were injected with 2 mg of aflibercept on a monthly basis for three months followed by bimonthly injections for another nine months. Measures of patients’ vision-related quality of life and best corrected visual acuity (BCVA), ophthalmic examinations, optical coherence tomography (OCT), and fluorescein angiography (FA) were performed on a regular basis. Indocyanine green (ICG) studies were also performed at baseline, 4 month, and 12 months. In addition to the study schedule, patients also received injections when needed in the case of disease progression or recurrence. Patients were classified into two categories based on OCT changes at 4 months: responders (OCT reduction of PED size ≥ 25%) or partial responders (OCT measured reduction of PED size < 25%).Of the 37 eyes included in the study, 27 (73.0%) were responders to aflibercept injections. The authors showed that PED height reduction was significantly different even after receiving one injection when comparing responders to partial responders. On average at 2 months (after 1 injection), PED height was 336.5 µm in responders compared with 63.9 µm in partial responders and at 12 months, PED height reduction was 348.6 µm in responders vs. 94.5 µm in partial responders. Similarly, after 12 months of injections, the BCVA of patients had an average gain of 10.1 ETDRS letters, with 14.0 letters in responders versus 0.5 letters in partial responders. At the end of one year, complete resolution of the PED was achieved in about one-third (32.3%) of patients. One patient, who had the largest PED (1009 µm), suffered a retinal tear, otherwise there were no other complications.Similar to the current study, previous retrospective studies have also shown a decrease in PED height after aflibercept use.4He L. Silva R.A. Moshfeghi D.M. Blumenkranz M.S. Leng T. Aflibercept for the treatment of retinal pigment epithelial detachments.Retina. 2016; 36: 492-498Crossref PubMed Scopus (19) Google Scholar, 5Hata M. Oishi A. Tsujikawa A. et al.Efficacy of intravitreal injection of aflibercept in neovascular age-related macular degeneration with or without choroidal vascular hyperpermeability.Invest Ophthalmol Vis Sci. 2014; 55: 7874-7880Crossref PubMed Scopus (44) Google Scholar Furthermore, two prospective studies showed a reduction in PED size when patients were switched to aflibercept after failing ranibizumab treatment.6Hatz K. Prunte C. Intravitreal aflibercept in neovascular age-related macular degeneration with limited response to ranibizumab: a treat-and-extend trial.Retina. 2017; 37: 1185-1192Google Scholar, 7Kocak I. Intravitreal aflibercept in treatment-resistant pigment epithelial detachment.Int Ophthalmol. 2017; 37: 531-537Google Scholar In addition to the decrease in PED height, Diaconita et al. found significant vision gain in patients receiving aflibercept. As noted by the authors, some of the limitations of this study include small sample size and lack of control group. Overall, the study provides valuable evidence for the use of aflibercept in the treatment of nAMD associated PEDs, and it suggests that patients who show good initial response (responders) after 3 injections will likely have significantly better final outcomes compared with patients who do not show much improvement (partial responders). However, further studies are required to better understand treatment response.Clinical practice point: Aflibercept shows significant promise in the improvement of visual acuity and reduction of PED height in the setting of nAMD. Patients who show good OCT response through the reduction of PED height after the first couple of injections of aflibercept will likely have better final outcomes compared with patients who do not respond initially.Referenced article: https://www.canadianjournalofophthalmology.ca/article/S0008-4182(18)30799-3/fulltext Age-related macular degeneration (AMD) is one of the leading causes of blindness. Pigment epithelial detachments (PED) can accompany neovascular AMD (nAMD) in as many as 62% of patients.1Coscas F. Coscas G. Souied E. Tick S. Soubrane G. Optical coherence tomography identification of occult choroidal neovascularization in age-related macular degeneration.Am J Ophthalmol. 2007; 144: 529-599Google Scholar PEDs are thought to be formed by the accumulation of fluid, blood, drusenoid material or fibrovascular tissue, which separates the retinal pigment epithelium from Bruch's membrane.2Pepple K. Mruthyunjaya P. Retinal pigment epithelial detachments in age-related macular degeneration: classification and therapeutic options.Semin Ophthalmol. 2011; 26 (5. Holz FG, Pauleikhoff D, Klein R, Bird AC): 198-208Crossref PubMed Scopus (34) Google Scholar Anti-VEGF treatment has become the mainstay of treatment for neovascular AMD. However, there is a paucity in the literature on the effects of aflibercept on PEDs secondary to nAMD. In this issue, Diaconita et al. (2019) report on their prospective, exploratory, open-label study aimed at understanding the effects of intravitreal aflibercept in treating patients with PED secondary to nAMD.3Diconita V. Li B. Pal L. Bahnacy F. Gonder J.R. Prospective evaluation of aflibercept in the treatment of pigment epithelial detachments secondary to neovascular age related macular degeneration.Can J Ophthalmol. 2019; 54: 626-634Google Scholar The authors recruited 36 patients (37 eyes) who were ≥55 years of age with PEDs secondary to nAMD and no previous anti-VEGF injections. Patients were injected with 2 mg of aflibercept on a monthly basis for three months followed by bimonthly injections for another nine months. Measures of patients’ vision-related quality of life and best corrected visual acuity (BCVA), ophthalmic examinations, optical coherence tomography (OCT), and fluorescein angiography (FA) were performed on a regular basis. Indocyanine green (ICG) studies were also performed at baseline, 4 month, and 12 months. In addition to the study schedule, patients also received injections when needed in the case of disease progression or recurrence. Patients were classified into two categories based on OCT changes at 4 months: responders (OCT reduction of PED size ≥ 25%) or partial responders (OCT measured reduction of PED size < 25%). Of the 37 eyes included in the study, 27 (73.0%) were responders to aflibercept injections. The authors showed that PED height reduction was significantly different even after receiving one injection when comparing responders to partial responders. On average at 2 months (after 1 injection), PED height was 336.5 µm in responders compared with 63.9 µm in partial responders and at 12 months, PED height reduction was 348.6 µm in responders vs. 94.5 µm in partial responders. Similarly, after 12 months of injections, the BCVA of patients had an average gain of 10.1 ETDRS letters, with 14.0 letters in responders versus 0.5 letters in partial responders. At the end of one year, complete resolution of the PED was achieved in about one-third (32.3%) of patients. One patient, who had the largest PED (1009 µm), suffered a retinal tear, otherwise there were no other complications. Similar to the current study, previous retrospective studies have also shown a decrease in PED height after aflibercept use.4He L. Silva R.A. Moshfeghi D.M. Blumenkranz M.S. Leng T. Aflibercept for the treatment of retinal pigment epithelial detachments.Retina. 2016; 36: 492-498Crossref PubMed Scopus (19) Google Scholar, 5Hata M. Oishi A. Tsujikawa A. et al.Efficacy of intravitreal injection of aflibercept in neovascular age-related macular degeneration with or without choroidal vascular hyperpermeability.Invest Ophthalmol Vis Sci. 2014; 55: 7874-7880Crossref PubMed Scopus (44) Google Scholar Furthermore, two prospective studies showed a reduction in PED size when patients were switched to aflibercept after failing ranibizumab treatment.6Hatz K. Prunte C. Intravitreal aflibercept in neovascular age-related macular degeneration with limited response to ranibizumab: a treat-and-extend trial.Retina. 2017; 37: 1185-1192Google Scholar, 7Kocak I. Intravitreal aflibercept in treatment-resistant pigment epithelial detachment.Int Ophthalmol. 2017; 37: 531-537Google Scholar In addition to the decrease in PED height, Diaconita et al. found significant vision gain in patients receiving aflibercept. As noted by the authors, some of the limitations of this study include small sample size and lack of control group. Overall, the study provides valuable evidence for the use of aflibercept in the treatment of nAMD associated PEDs, and it suggests that patients who show good initial response (responders) after 3 injections will likely have significantly better final outcomes compared with patients who do not show much improvement (partial responders). However, further studies are required to better understand treatment response. Clinical practice point: Aflibercept shows significant promise in the improvement of visual acuity and reduction of PED height in the setting of nAMD. Patients who show good OCT response through the reduction of PED height after the first couple of injections of aflibercept will likely have better final outcomes compared with patients who do not respond initially. Referenced article: https://www.canadianjournalofophthalmology.ca/article/S0008-4182(18)30799-3/fulltext Identifying a retrobulbar hematoma on orbital imaging: should we worry?A retrobulbar hemorrhage is an uncommon yet potentially sight-threatening complication following orbital trauma or surgery. If the hemorrhage or associated orbital edema leads to an acute rise in orbital pressure, a compartment syndrome can develop and compromise perfusion to the retina and optic nerve.1Kondoff M. Nassrallah G. Ross M. Deschenes J. Incidence and outcomes of retrobulbar hematoma diagnosed by computed tomography in cases of orbital fracture.Can J Ophthalmol. 2019; 54: 606-610Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar A large study described a remaining visual acuity of 20/100 or worse in over a third of patients with orbital compartment syndrome, even despite successful canthotomy and cantholysis procedures.2Fattahi T. Brewer K. Retana A. Ogledzki M. Incidence of retrobulbar hemorrhage in the emergency department.J Oral Maxillofac Surg. 2014; 72: 2500-2502Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar The importance of remaining vigilant about the possibility of raised orbital pressure is highlighted by a short 1- to 2-hour interval following trauma where intervention might be effective in restoring vision.3Soare S. Foletti J.M. Gallucci A. Collet C. Guyot L. Chossegros C. Update on orbital decompression as emergency treatment of traumatic blindness.J Craniomaxillofac Surg. 2015; 43: 1000-1003Crossref PubMed Scopus (16) Google ScholarWhile strategies for intervening in cases of suspected orbital compartment syndrome have been well described,2Fattahi T. Brewer K. Retana A. Ogledzki M. Incidence of retrobulbar hemorrhage in the emergency department.J Oral Maxillofac Surg. 2014; 72: 2500-2502Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 3Soare S. Foletti J.M. Gallucci A. Collet C. Guyot L. Chossegros C. Update on orbital decompression as emergency treatment of traumatic blindness.J Craniomaxillofac Surg. 2015; 43: 1000-1003Crossref PubMed Scopus (16) Google Scholar, 4Sun M.T. Chan W.O. Selva D. Traumatic orbital compartment syndrome: importance of the lateral canthomy and cantholysis.Emerg Med Australas. 2014; 26: 274e278Google Scholar there is little guidance on how to manage a retrobulbar hemorrhage identified on orbital imaging. In this issue, Kondoff et al. eloquently address this knowledge gap.1Kondoff M. Nassrallah G. Ross M. Deschenes J. Incidence and outcomes of retrobulbar hematoma diagnosed by computed tomography in cases of orbital fracture.Can J Ophthalmol. 2019; 54: 606-610Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar The authors conducted a 3-year retrospective review of 256 patients with orbital fractures referred for an ophthalmic assessment. Retrobulbar hemorrhages were identified in nearly one-third of all cases of orbital fractures imaged by computed tomography (CT) of the facial bones. Of these cases, however, only one developed a clinical orbital compartment syndrome and required urgent medical and surgical intervention.1Kondoff M. Nassrallah G. Ross M. Deschenes J. Incidence and outcomes of retrobulbar hematoma diagnosed by computed tomography in cases of orbital fracture.Can J Ophthalmol. 2019; 54: 606-610Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar In addition, of those patients where follow-up data was available, none of those with CT evidence of retrobulbar hemorrhage went on to later develop orbital compartment syndrome. As a result, the authors conclude that a retrobulbar hemorrhage identified radiographically, in the absence of other clinical findings, is unlikely to develop into a sight-threatening orbital compartment syndrome.Given the urgency in diagnosing an orbital compartment syndrome, exploring how to approach the radiographic finding of retrobulbar hemorrhage has significant clinical importance. The nearly one-third of fracture cases associated with orbital hemorrhage identified in this study, however, is surprisingly high. This may be explained by the authors using cases from a database of patients who required close follow-up. In support of this, a previous study did not identify a retrobulbar hemorrhage in 65 cases referred with orbital fracture.5Ross M. El-Haddad C. Deschênes J. Ocular injury in orbital fractures at a level I trauma center.Can J Ophthalmol. 2017; 52: 499-502Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Nevertheless, the question of how to manage a radiographic finding of a retrobulbar hemorrhage in this setting is not uncommon. Knowing that approximately 1% of these cases develop orbital compartment syndrome is very useful and further supports raised orbital pressure being a clinical diagnosis.Finally, by exploring factors associating orbital fractures with retrobulbar hemorrhage, the possibility exists for classifying a type of fracture or hemorrhage as higher or lower risk for developing orbital compartment syndrome. Despite the low frequency of orbital compartment syndrome in radiographically identified retrobulbar hemorrhage in general, clinical features such as fracture location, anticoagulation use, and hematoma size may be important in guiding how closely these patients need to be followed.In summary, Kondoff et al. have provided evidence that a retrobulbar hemorrhage identified on CT imaging is not very specific for raised orbital pressure in patients with an orbital fracture. This finding reassures practitioners that orbital compartment syndrome remains a clinical diagnosis.Referenced article: https://www.canadianjournalofophthalmology.ca/article/S0008-4182(18)30862-7/fulltext A retrobulbar hemorrhage is an uncommon yet potentially sight-threatening complication following orbital trauma or surgery. If the hemorrhage or associated orbital edema leads to an acute rise in orbital pressure, a compartment syndrome can develop and compromise perfusion to the retina and optic nerve.1Kondoff M. Nassrallah G. Ross M. Deschenes J. Incidence and outcomes of retrobulbar hematoma diagnosed by computed tomography in cases of orbital fracture.Can J Ophthalmol. 2019; 54: 606-610Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar A large study described a remaining visual acuity of 20/100 or worse in over a third of patients with orbital compartment syndrome, even despite successful canthotomy and cantholysis procedures.2Fattahi T. Brewer K. Retana A. Ogledzki M. Incidence of retrobulbar hemorrhage in the emergency department.J Oral Maxillofac Surg. 2014; 72: 2500-2502Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar The importance of remaining vigilant about the possibility of raised orbital pressure is highlighted by a short 1- to 2-hour interval following trauma where intervention might be effective in restoring vision.3Soare S. Foletti J.M. Gallucci A. Collet C. Guyot L. Chossegros C. Update on orbital decompression as emergency treatment of traumatic blindness.J Craniomaxillofac Surg. 2015; 43: 1000-1003Crossref PubMed Scopus (16) Google Scholar While strategies for intervening in cases of suspected orbital compartment syndrome have been well described,2Fattahi T. Brewer K. Retana A. Ogledzki M. Incidence of retrobulbar hemorrhage in the emergency department.J Oral Maxillofac Surg. 2014; 72: 2500-2502Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 3Soare S. Foletti J.M. Gallucci A. Collet C. Guyot L. Chossegros C. Update on orbital decompression as emergency treatment of traumatic blindness.J Craniomaxillofac Surg. 2015; 43: 1000-1003Crossref PubMed Scopus (16) Google Scholar, 4Sun M.T. Chan W.O. Selva D. Traumatic orbital compartment syndrome: importance of the lateral canthomy and cantholysis.Emerg Med Australas. 2014; 26: 274e278Google Scholar there is little guidance on how to manage a retrobulbar hemorrhage identified on orbital imaging. In this issue, Kondoff et al. eloquently address this knowledge gap.1Kondoff M. Nassrallah G. Ross M. Deschenes J. Incidence and outcomes of retrobulbar hematoma diagnosed by computed tomography in cases of orbital fracture.Can J Ophthalmol. 2019; 54: 606-610Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar The authors conducted a 3-year retrospective review of 256 patients with orbital fractures referred for an ophthalmic assessment. Retrobulbar hemorrhages were identified in nearly one-third of all cases of orbital fractures imaged by computed tomography (CT) of the facial bones. Of these cases, however, only one developed a clinical orbital compartment syndrome and required urgent medical and surgical intervention.1Kondoff M. Nassrallah G. Ross M. Deschenes J. Incidence and outcomes of retrobulbar hematoma diagnosed by computed tomography in cases of orbital fracture.Can J Ophthalmol. 2019; 54: 606-610Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar In addition, of those patients where follow-up data was available, none of those with CT evidence of retrobulbar hemorrhage went on to later develop orbital compartment syndrome. As a result, the authors conclude that a retrobulbar hemorrhage identified radiographically, in the absence of other clinical findings, is unlikely to develop into a sight-threatening orbital compartment syndrome. Given the urgency in diagnosing an orbital compartment syndrome, exploring how to approach the radiographic finding of retrobulbar hemorrhage has significant clinical importance. The nearly one-third of fracture cases associated with orbital hemorrhage identified in this study, however, is surprisingly high. This may be explained by the authors using cases from a database of patients who required close follow-up. In support of this, a previous study did not identify a retrobulbar hemorrhage in 65 cases referred with orbital fracture.5Ross M. El-Haddad C. Deschênes J. Ocular injury in orbital fractures at a level I trauma center.Can J Ophthalmol. 2017; 52: 499-502Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Nevertheless, the question of how to manage a radiographic finding of a retrobulbar hemorrhage in this setting is not uncommon. Knowing that approximately 1% of these cases develop orbital compartment syndrome is very useful and further supports raised orbital pressure being a clinical diagnosis. Finally, by exploring factors associating orbital fractures with retrobulbar hemorrhage, the possibility exists for classifying a type of fracture or hemorrhage as higher or lower risk for developing orbital compartment syndrome. Despite the low frequency of orbital compartment syndrome in radiographically identified retrobulbar hemorrhage in general, clinical features such as fracture location, anticoagulation use, and hematoma size may be important in guiding how closely these patients need to be followed. In summary, Kondoff et al. have provided evidence that a retrobulbar hemorrhage identified on CT imaging is not very specific for raised orbital pressure in patients with an orbital fracture. This finding reassures practitioners that orbital compartment syndrome remains a clinical diagnosis. Referenced article: https://www.canadianjournalofophthalmology.ca/article/S0008-4182(18)30862-7/fulltext Beware of stripped-down results: periadventitial pathology in temporal artery biopsiesTemporal artery biopsy is the gold standard for diagnosis of giant cell arteritis (GCA), with pathology specimens showing mononuclear cell infiltrates, disruption of the internal elastic lamina, intimal hyperplasia and multinucleated giant cells. False negative results do occur,1Allsop C.J. Gallagher P.J. Temporal artery biopsy in giant-cell arteritis. A reappraisal.Am J Surg Pathol. 1981; 5: 317-323Crossref PubMed Scopus (123) Google Scholar which is largely attributed to the discontinuous nature of arteritic involvement producing skip lesions. Because of this, a minimum biopsy length of 2 cm is recommended. As McDonald, Farmer, and Blanco point out in their case series published in this month's issue, there are no guidelines regarding stripped specimens versus inclusion of periadventitial tissue, which may be overlooked as a valuable source of information.2McDonald H. Farmer J.P. Blanco P.L. Periadventitial tissue examination in temporal artery biopsies for suspected giant cell arteritis: a case series and literature review.Can J Ophthalmol. 2019; 54: 615-620Abstract Full Text Full Text PDF Scopus (4) Google ScholarSix cases of patients undergoing bilateral temporal artery biopsies for evaluation of GCA were included where surrounding tissue showed evidence of pathology. Four of the six did not show any evidence of inflammatory changes in the main temporal artery itself. Five patients had an alternate diagnosis based on small vessel changes within the periadventitia: two with pANCA-positive small vessel vasculitis, one with eosinophilic granulomatosis with polyangiitis (EGPA), one with nonspecific small vessel vasculitis, and one with chronic lymphocytic leukemia coincident with GCA. The sixth patient was determined to have GCA, however, only a small branch of the main temporal artery was positive for arteritis.There has been increasing interest in diagnosis of GCA using non-invasive imaging techniques. MRI and MR angiography allow for simultaneous visualization of the bilateral temporal arteries as well as extra- and intracranial vessels with high sensitivity and specificity for GCA.3Klink T. Geiger J. Both M. Ness T. Heinzelmann S. Reinhard M. et al.Giant cell arteritis: diagnostic accuracy of MR imaging of superficial cranial arteries in initial diagnosis-results from a multicenter trial.Radiology. 2014; 273: 844-852Crossref PubMed Scopus (118) Google Scholar, 4Rhéaume M. Rebello R. Pagnoux C. Carette S. Clements-Baker M. Cohen-Hallaleh V. et al.High-Resolution Magnetic Resonance Imaging of Scalp Arteries for the Diagnosis of Giant Cell Arteritis: Results of a Prospective Cohort Study.Arthritis Rheumatol. 2017; 69: 161-168Crossref PubMed Scopus (62) Google Scholar A recent meta-analysis of the use of temporal artery ultrasound in GCA reported sensitivity and specificity of 68% and 81% respectively for a hypoechoic “halo sign.”5Rinagel M. Chatelus E. Jousse-Joulin S. Sibilia J. Gottenberg J.E. Chasset F. et al.Diagnostic performance of temporal artery ultrasound for the diagnosis of giant cell arteritis: a systematic review and meta-analysis of the literature.Autoimmun Rev. 2019; 18: 56-61Crossref PubMed Scopus (61) Google Scholar The current study highlights the importance of tissue diagnosis, as not all inflammatory changes detected through imaging of the temporal arteries will be due to GCA. It is important to distinguish between GCA and other forms of vasculitis as the organ system involvement, prognosis and management differ. Biopsy findings led to a change in management in several of the cases described in the current work. In addition, isolated small vessel changes are unlikely to be captured using these imaging modalities. Although GCA is classically described as a medium- and large-vessel vasculitis, small vessel vasculitis is present in most temporal artery biopsy specimens and, as in the current study, may be the only histological evidence of inflammatory pathology.6Belilos E. Maddox J. Kowalewski R.M. Kowalewska J. Turi G.K. Nochomovitz L.E. et al.Temporal small-vessel inflammation in patients with giant cell arteritis: clinical course and preliminary immunohistopathologic characterization.J Rheumatol. 2011, Feb; 38: 331-338Google Scholar, 7Esteban M.J. Font C. Hernández-Rodríguez J. Valls-Solé J. Sanmartí R. Cardellach F. et al.Small-vessel vasculitis surrounding a spared temporal artery: clinical and pathological findings in a series of twenty-eight patients.Arthritis Rheum. 2001, Jun; 44: 1387-1395Crossref PubMed Scopus (91) Google ScholarOne limitation of this work is that it is not clear whether the clinical picture for each patient was consistent with GCA, or whether the patients with alternate diagnoses after biopsy had displayed features suggestive of other etiologies that were missed. The importance of history and physical examination in the work-up of vasculitis must not be underestimated. The initial diagnosis of GCA and decision to initiate steroid treatment must be made based on clinical assessment as one cannot afford to wait for biopsy results and risk permanent vision loss or other serious complications.Given the variability in the extent and type of arteritis produced by this condition, there will always be patients diagnosed as “biopsy-negative GCA.” However, it would certainly be prudent to do everything possible to maximize yield of a temporal artery biopsy. The results of the current study taken together with the literature evidence for isolated small vessel disease in GCA strongly suggests that when biopsy is indicated, inclusion of periadventitial tissue should be the standard for submitting temporal artery specimens. This would be particularly important in cases where clinical presentation is unclear, or not classic for GCA.Referenced article: https://www.canadianjournalofophthalmology.ca/article/S0008-4182(18)31110-4/fulltext Temporal artery biopsy is the gold standard for diagnosis of giant cell arteritis (GCA), with pathology specimens showing mononuclear cell infiltrates, disruption of the internal elastic lamina, intimal hyperplasia and multinucleated giant cells. False negative results do occur,1Allsop C.J. Gallagher P.J. Temporal artery biopsy in giant-cell arteritis. A reappraisal.Am J Surg Pathol. 1981; 5: 317-323Crossref PubMed Scopus (123) Google Scholar which is largely attributed to the discontinuous nature of arteritic involvement producing skip lesions. Because of this, a minimum biopsy length of 2 cm is recommended. As McDonald, Farmer, and Blanco point out in their case series published in this month's issue, there are no guidelines regarding stripped specimens versus inclusion of periadventitial tissue, which may be overlooked as a valuable source of information.2McDonald H. Farmer J.P. Blanco P.L. Periadventitial tissue examination in temporal artery biopsies for suspected giant cell arteritis: a case series and literature review.Can J Ophthalmol. 2019; 54: 615-620Abstract Full Text Full Text PDF Scopus (4) Google Scholar Six cases of patients undergoing bilateral temporal artery biopsies for evaluation of GCA were included where surrounding tissue showed evidence of pathology. Four of the six did not show any evidence of inflammatory changes in the main temporal artery itself. Five patients had an alternate diagnosis based on small vessel changes within the periadventitia: two with pANCA-positive small vessel vasculitis, one with eosinophilic granulomatosis with polyangiitis (EGPA), one with nonspecific small vessel vasculitis, and one with chronic lymphocytic leukemia coincident with GCA. The sixth patient w