Cameron F. Parsa

Central corneal thickness and correlation to optic disc size: a potential link for susceptibility to glaucoma

Aims: To evaluate a possible relationship between central corneal thickness (CCT) and optic disc area in patients with primary open-angle glaucoma (POAG). Methods: Patients with POAG underwent eye examination, optic disc imaging with the Heidelberg Retina Tomograph II (HRT II) and ultrasound corneal pachymetry. Exclusion criteria were prior ocular surgery and low-quality HRT II images (HRT standard deviation (SD) >50). Pearson’s correlation coefficients were calculated to assess the associations between CCT and optic disc area. Results: 212 eyes of 137 patients with POAG were examined. In all, 66 (48%) subjects were women, 104 (76%) were Caucasian, 26 (19%) African-American and 7 (5%) other races. 72 eyes remained after excluding those with prior intraocular surgery and low-quality HRT II images. In a univariate analysis of this group, CCT was inversely correlated with optic disc surface area (Pearson’s correlation coefficient r = −0.284, p = 0.036, n = 72). Mean (SD) disc area was 2 (0.53) mm2 (n = 160). Caucasians had significantly smaller discs (p<0.001) than other races (Caucasian 1.9 (0.47) mm2 (n = 119), African-Americans 2.4 (0.54) mm2 (n = 31), other races 2.3 (0.45) mm2 (n = 10)). Conclusion: CCT is inversely correlated to optic disc area. Although thicker corneas have been recognised to cause slight overestimation of true intraocular pressure (IOP), they may also indicate the presence of a substantially smaller, and thus more robust, optic nerve head. People with thinner corneas which slightly underestimate the true IOP may also have larger and more deformable optic discs.

Redefining papillorenal syndrome: an underdiagnosed cause of ocular and renal morbidity.

PURPOSE To report ocular and renal findings specific to the inheritable entity called papillorenal (also known as renal-coloboma) syndrome and relate these to a common cause. DESIGN Observational case series and genetic study. PARTICIPANTS Two unrelated probands presenting with absent central retinal vessels and 11 available family members. TESTING Doppler ultrasonographic imaging of the optic nerves and kidneys, fluorescein angiography, and genetic testing for PAX2 mutations were performed. In selected cases, indocyanine green angiography, scanning laser ophthalmoscope perimetry, Retinal Thickness Analyzer measurements, visual evoked potentials, and magnetic resonance imaging were also performed. MAIN OUTCOME MEASURES Better defined characteristics of the papillorenal syndrome. RESULTS Numerous cilioretinal vessels were present with rudimentary or absent central retinal vessels. Superonasal visual field defects, typical for papillorenal syndrome, corresponded to inferotemporal areas of anomalous retinal and choroidal perfusion and hypoplastic retina. Renal hypoplasia was discovered in two affected members of one family (with previously unsuspected renal failure in one case), and recurrent pyelonephritis was discovered in four affected members of the other family. No PAX2 mutations were detected. CONCLUSIONS In the papillorenal syndrome, the hereditary absence of central retinal vessels may be missed, leading to confusion with isolated coloboma, low-tension glaucoma, and morning glory anomaly. Greater awareness of this syndrome will avoid unneeded glaucoma therapy, allow earlier recognition of renal diseases, and allow genetic counseling. We propose that the papillorenal syndrome is a primary dysgenesis that causes vascular abnormalities predominantly affecting the eye, kidney, and urinary tract, leading to hypoplasia of these structures. The absence of defects in the PAX2 gene in these families suggests that mutations in other genes may also be responsible for this syndrome.

Juvenile pilocytic astrocytomas do not undergo spontaneous malignant transformation: grounds for designation as hamartomas

Aim: To determine whether juvenile pilocytic astrocytomas WHO grade I have the potential for spontaneous malignant transformation. Methods: A literature search was performed, cross-referencing juvenile pilocytic astrocytoma, pilocytic astrocytoma, astrocytoma grade I, optic glioma, glioma, low-grade gliomas, polar spongioblastoma, gliocytoma embryonale, and malignant transformation, anaplasia or anaplastic change. Bibliographic PubMed and Google searches were performed, and reference ophthalmology and neuropathology textbooks were utilised. Results: A total of 52 purported cases of malignant transformation were found. Twenty-two of these tumours, however, did not initially match criteria for juvenile pilocytic astrocytoma WHO grade I and were excluded. Six other cases were located within the irradiated field but represented anaplasias developing independently of the primary tumour. The remaining 24 malignancies had all been previously irradiated. Conclusion: Juvenile pilocytic astrocytomas WHO grade I do not undergo spontaneous anaplastic transformation. Malignant transformations have only been demonstrated following radiation therapy. Earlier clinical and histopathological opinions regarding juvenile pilocytic astrocytomas as hamartomatous lesions are reaffirmed.

Calf Lung Surfactant Extract Prophylaxis and Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is an important cause of blindness among extremely low birth weight infants (birth weight less than or equal to 1000 g). In the 1990s, greater numbers of extremely low birth weight infants will survive, in part due to routine surfactant replacement therapy for neonatal respiratory distress syndrome. Few studies have evaluated the effect of surfactant therapy on the incidence and severity of ROP. The authors performed a review of the records of extremely low birth weight infants born in two 2-year intervals before and after initiation of a clinical protocol in which all extremely low birth weight infants received prophylactic treatment with calf lung surfactant extract (Infasurf). Surfactant therapy was associated with a significant improvement in survival to discharge (79% [88 of 112] versus 63% [82 of 131]; P = 0.01). Compared with control infants, surfactant-treated infants had a significantly lower incidence of any stage of ROP (64% [56 of 87] versus 85% [68 of 80]; P less than 0.004). The incidence of threshold (Stage 3 plus or greater) ROP was substantially reduced (3.4% [3 of 87] versus 10% [8 of 80]; P = 0.16)). The surfactant-associated reduction in ROP was independent of birth weight, gestational age, race, or sex. These data suggest that Infasurf may substantially reduce the incidence and severity of ROP in the extremely low birth weight population.

Nonarteritic anterior ischemic optic neuropathy (NAION): a misnomer. Rearranging pieces of a puzzle to reveal a nonischemic papillopathy caused by vitreous separation.

Nonarteritic anterior ischemic optic neuropathy (NAION) has been the subject of numerous publications and editorials. Yet, meaningful progress toward understanding the pathogenesis of this entity has been limited. As the term “ischemic” would indicate, investigators have focused their efforts on defending a vascular cause. What is the evidence for ischemia in this entity that, by histopathologic and observational ophthalmology, first affects the prelaminar optic disc? The fact that vascular abnormalities such as disc hemorrhages and swelling are present at the time of visual loss, followed by peripapillary vascular narrowing and ensuing disc pallor, is enticing, but not etiologically conclusive. Unlike ischemic neuropathy in giant cell arteritis in which short posterior ciliary arteries are affected, with loss of supplied tissue leading to increased laminar cupping, such findings have never been demonstrated in NAION. Fluorescein and indocyanine green angiography demonstrate changes at the prelaminar disc surface alone, uncorrelated to changes in visual field or in neural tissue, and not at the deeper levels supplied by the ciliochoroidal and central retinal vasculature. Whiteness with disc swelling has been accepted as a sign of ischemia, but there is both optic disc and retinal evidence that such whiteness is indicative of axoplasmic stasis (cotton wool spots) that may also occur simply from anatomic distortion of axons rather than occlusion of vessels. This may also occur from fracture of the axonal cytoskeleton and frank membrane disruption with axoplasmic “leakage.” In giant cell arteritis, retrolaminar vascular occlusion will cause axoplasmic accumulation anteriorly, with a white appearance at the level of the optic disc. If disc ischemia were prelaminar, however, white axoplasmic accumulation and swelling would develop upstream predominately in peripapillary retina. The immediate development of prelaminar disc changes with the onset of clinical symptomatology precludes slow orthograde axoplasmic accumulation as responsible. The search for a systemic vascular denominator for this disease has been futile. With so little to show for it, it seems worth questioning the underlying presumption of ischemia as an etiologic factor for so-called NAION. When the name of an entity itself may be a misnomer, it can be especially difficult to escape erroneous interpretations of pathophysiology. Indeed, the mechanism of this disease needs to be reanalyzed in a completely different direction.

Why Visual Function Does Not Correlate With Optic Glioma Size or Growth

(Drs Han, Rha, and Carroll and Messrs Croskrey and Schroeder), Cel l Biology, Neurobiology, and A n a t o m y ( M r D u b i s a n d D r C a r r o l l ) , a n d Biophysics (Dr Carroll), Medical College of Wisconsin, Milwaukee. Correspondence: Dr Han, Department of Ophthalmology, Medical College of Wisconsin, 925 N 87th St, Milwaukee, WI 53226 (dhan@mcw.edu). Author Contributions: Dr Han had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Financial Disclosure: None reported. Funding/Support: This work was supported by grants P30EY001931, T32EY014537, and R01EY017607 from the National Institutes of Health, an unrestricted departmental grant from Research to Prevent Blindness, the Thomas M. Aaberg Sr Retina Research Fund, and the Jack A. and Elaine D. Klieger Professorship in Ophthalmology (Dr Han). Mr Croskrey is the recipient of a Career Development Award from Research to Prevent Blindness. Temporary use of the Pascal laser was provided by OptiMedica Corp. This investigation was conducted in a facility constructed with support from grant C06 RR-RR016511 from the Research Facilities Improvement Program, National Center for Research Resources, National Institutes of Health. Online-Only Material: The eFigures are available at http: //www.archophthalmol.com. Additional Contributions: Alfredo Dubra, PhD, designed the AOSO and Phyllis Summerfelt provided technical/administrative assistance in figure preparation.

Effect of a Single Application of Pulsed Dye Laser Treatment of Port-wine Birthmarks on Intraocular Pressure

BACKGROUND A new pathophysiologic mechanism has been proposed that indicates that periorbital port-wine birthmarks (PWBs) serve as alternate collateral blood passageways when orbital venous drainage is impaired. The occlusion of such collateral venous channels could, therefore, potentially exacerbate impaired ocular venous flow and trigger the development or worsening of glaucoma in patients with Sturge-Weber syndrome. We investigated to what extent a single application of laser therapy, which occludes only the most superficial portions of a facial PWB, might affect intraocular pressure. Pressures before and after laser treatment were measured to determine pressure difference in 15 patients receiving laser treatment. OBSERVATIONS The greatest pressure differences were observed in patients with a PWB closest to the eye (P = .02). Posttreatment pressures were significantly decreased, relative to pretreatment pressures, only in patients with a PWB on the eyelid compared with patients with a facial PWB not near the eyes (2.33 vs 0.75 mm Hg; P = .004). No correlation was found between change in pressure and patient age, PWB size, or number of previous treatments. CONCLUSIONS A single laser application to a PWB does not appear to show a clinically relevant change in intraocular pressure. Further study is needed longitudinally in a broad range of patients.

Diagnosing papillorenal syndrome: see the optic papilla

Sirs, In their article “A clinico-genetic study of renal coloboma syndrome in children”, Cheong and colleagues accurately point out that a variety of PAX2 mutations, one of which they had discovered, can cause the described phenotype of associated ocular, renal and urinary tract anomalies seen in this autosomal dominant condition [1]. However, it should also be noted that many patients with the “renal coloboma” disorder do not have any identifiable mutations in the PAX2 gene [2, 3]. The syndrome is not defined by PAX2 genetic analysis, but by clinical findings. Cheong and co-workers employed the syndrome’s older “renal-coloboma” nomenclature [1] as opposed to the subsequent “papillorenal” designation. Precise language is important in this case, since confusion created by the term “coloboma” has led many investigators to consider incomplete closure of the embryonic optic fissure to be the cause of an optic nerve anomaly in cases where there is no supportive evidence for such an etiology [2]. Accordingly, the preferred OMIM appellation now is “papillorenal syndrome” [4] (OMIM #120330). It should be noted that the prefix “papillo” indicates the optic papilla as the site of the ocular abnormality and not that of the renal papillae. While the term “papillorenal” is also not fully descriptive of all the possible associated ocular or urinary tract anomalies (such as vesicoureteral reflux), it avoids the misnomer of “coloboma” and implications, thereof, of an unrelated pathophysiologic pathway. Cheong et al. correctly emphasize that there is considerable variability of ocular and urinary tract findings [1]. Among that variability, however, one constant feature exists and is clearly visible in the ocular fundus photographs they published: the lack of central retinal blood supply. Instead of central vessels within the optic papilla, the disc is variably excavated centrally; the cilioretinal vessels originate outside and at the periphery of the optic nerve supplying the retina (“vacant discs”). These disc vessels circumferentially make hairpin turns over the neuroretinal rim toward the retina. Though often asymptomatic, the absence of central retinal vasculature can be associated with retinal hypoplasia, causing visual field defects. In some instances, this can lead to secondary serous retinal detachments [5] which, if occurring early in development, can lead to relative microphthalmia. This bilaterally visible vascular anomaly of the optic papilla testifies to a systemically deficient process of angiogenesis (as opposed to vasculogenesis) [6]. Angiogenesis is most critical to the development of both eye and kidney, the most perfused tissues per gram weight of the human body. Angiogenic factors are involved in the budding of vascular endothelial cells from pre-existing vessels laid down by vasculogenesis [6]. These same factors also affect the budding of other tubular structures Pediatr Nephrol (2008) 23:1893–1894 DOI 10.1007/s00467-008-0870-6

Descemet Membrane Rupture Accompanied by Stromal Clefting in Congenital Glaucoma

Comment. Bevacizumab in this patient was shown to be well tolerated without any signs of toxic effects; in particular, no inflammation, degeneration, or necrosis was observed. Furthermore, the results show that bevacizumab effectively controlled the neovascularization in zone 1, stage 2 ROP. Vascular endothelial growth factor is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. The retina and the proliferating abnormal vessels showed high levels of VEGF expression at both messenger RNA and protein levels. Vascular endothelial growth factor has recently been shown to influence neuronal growth, differentiation, and survival owing to its neurotrophic effects. Therefore, the dosage of bevacizumab is critical to preserve this effect on the neuroretina for adequate development. In our case, we administered 40% of the adult dose twice. Our results show preservation of morphology and expression of VEGF in the retina.

Of Pax2 laboratory mice and human papillorenal investigations: maintaining the distinctions between cause and effect.

I n the article “Optic nerve axon number in mouse is regulated by Pax2” in this issue of Journal of AAPOS, Alur and coworkers accurately describe the papillorenal syndrome (OMIM 120330) as an autosomal-dominant disorder characterized by congenital optic nerve and kidney abnormalities. Precise language is important in this case, and the authors are careful to avoid using the alternative appellation and misnomer “renal-coloboma syndrome.” Confusion created by the term “coloboma” has led many investigators to consider incomplete closure of the embryonic optic fissure to be the cause of an optic nerve anomaly in cases in which there is no supportive evidence for such an etiology. Alur and coworkers note that a variety of PAX2 mutations have been found in patients with papillorenal syndrome. However, they neglect to specify that many, if not most, patients with the disorder do not have any identifiable mutations in the PAX2 gene. While overlooking the patients without PAX2 mutations, they infer that mutations in the PAX2 gene define the papillorenal syndrome and ignore the possibility that other gene disorders cause the condition. The papillorenal syndrome is defined not by PAX2 genetic analysis but by clinical findings, and these findings must be well characterized. Ocular fundus descriptions of “abnormal retinal blood vessel patterning,” “optic pits,” and “large excavations of the optic nerve head with reduced visual acuity” are imprecise and could lead to faulty assumptions. It is not the patterning of blood vessels per se that is abnormal in humans with this disorder; rather, the abnormality consists of the variable absence of the central retinal vasculature with commensurate enlargement of the cilioretinal vasculature at the level of the optic disk. Such an abnormality implicates a developmental defect of angiogenesis. Normally, angiogenesis serves to preserve and maintain the distal portion of the regressing hyaloid system, which eventually becomes the central retinal vasculature. Premature regression of such a central vascular scaffold may account for the variable central excavation of the disk. It is unrelated to the formation of optic pits,