Macular Damage Research Articles

Temporal Relation between Macular Ganglion Cell–Inner Plexiform Layer Loss and Peripapillary Retinal Nerve Fiber Layer Loss in Glaucoma

To investigate the temporal relationship between inferior macular ganglion cell-inner plexiform layer (mGCIPL) loss and corresponding peripapillary retinal nerve fiber layer (pRNFL) defect on the optical coherence tomography (OCT) deviation map in glaucoma. Retrospective, observational study. A total of 151 patients with early-stage glaucoma (visual field [VF] mean deviation between-1.5 and-5.5 decibels [dB]). Spectral-domain OCT mGCIPL and pRNFL deviation maps were obtained for the baseline (from January 2012 to August 2012) and again for the follow-up (from January 2015 to August 2015). An integrated deviation map thereafter was merged by vascular landmark-guided superimposition of mGCIPL and pRNFL deviation maps onto RNFL imagery. On the basis of an earlier schematic model, the inferotemporal peripapillary area was divided into (1) the macular vulnerability zone (MVZ) and (2) the inferoinferior portion. Temporal sequence of inferior mGCIPL loss and corresponding pRNFL (i.e.,pRNFL in MVZ) defect on integrated deviation map. At baseline, 99 (65.6%) of the 151 eyes showed inferior mGCIPL loss. In addition, 112 eyes (74.2%) and 5 eyes (3.3%) showed inferoinferior pRNFL defect and pRNFL defect in the MVZ, respectively. At the 3-year follow-up, 112 (74.2%) of the eyes showed inferior mGCIPL loss, whereas 123 eyes (81.5%) and 25 eyes (16.6%) showed inferoinferior pRNFL defect and pRNFL defect in the MVZ, respectively. Ninety-four eyes initially showed inferior mGCIPL loss without pRNFL defect in the MVZ; among them, 19 (20.2%) subsequently showed defect during the 3-year follow-up interval. Meanwhile, among the 52 eyes without preexisting inferior mGCIPL loss, only 1 (1.9%; P < 0.001) developed a pRNFL defect in the MVZ during the 3-year follow-up interval. In eyes with early glaucoma, mGCIPL change is frequently detected before corresponding pRNFL change. This could be the result of a superior sensitivity of mGCIPL deviation map that allows detection of an abnormality in the mGCIPL thickness earlier. In this light, OCT pRNFL analysis alone likely would overlook macular damage. Macular OCT imaging should be included in the imaging algorithm for the serial observation of patients with glaucoma.

Inferior Macular Damage in Glaucoma: Its Relationship to Retinal Nerve Fiber Layer Defect in Macular Vulnerability Zone.

The purpose of the study was to investigate the prevalence of abnormal thinning of the inferior macular ganglion cell-inner plexiform layer (mGCIPL) in glaucoma and to understand its relationship to abnormal regions of the peripapillary retinal nerve fiber layer (pRNFL), including the macular vulnerability zone (MVZ). We evaluated 186 eyes (186 patients) with glaucoma. An integrated deviation map was merged by superimposition of mGCIPL and pRNFL deviation maps (from a spectral-domain optical coherence tomography) onto RNFL photography as aligned by Photoshop software based on vascular landmarks. The peripapillary area was divided into 2 locations according to a previously suggested schematic model: (1) the MVZ; and (2) the inferoinferior portion. The key findings of the topographic analysis of mGCIPL and pRNFL deviation maps were as follows: (1) 145 of 186 eyes showed inferior mGCIPL loss; (2) if a defect existed in the MVZ of the pRNFL (63 eyes), there was also an inferior mGCIPL defect; (3) however, the other 82 eyes with inferior mGCIPL abnormalities showed an abnormal mGCIPL without a corresponding pRNFL defect in the MVZ. There was no single case of pRNFL defect in the MVZ without inferior mGCIPL loss. However, there were a few cases of inferior mGCIPL loss without pRNFL defect in the MVZ. These findings signify that detection of inferior mGCIPL loss might be earlier than that of pRNFL defect in the MVZ. Therefore, pRNFL analysis of the optical coherence tomography disc cube scan alone is insufficient for detection of early-stage glaucomatous damage.

Accidental macular injury with class IVb laser outside the medical settings

In the medical settings, safety precautions are used to mitigate inadvertent ocular damage due to laser beams. High power lasers are illegal in many countries; however, they are sometimes used on social occasions. Use by an untrained member of the public can result in severe accidental ocular damage. We report a case of macular damage and central visual loss due to the illegal use of a class IVb 2000mW power laser in a 20-year-old male. To our knowledge, this is the first case of macular injury due to this particular type of laser. The case history and management over a 6-month period is described. Pubic education initiatives are required to increase the awareness of the dangerous nature of laser beam exposure outside a medical setting.

PACAP and VIP Inhibit HIF-1α-Mediated VEGF Expression in a Model of Diabetic Macular Edema.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) exert a protective role against retinal injuries, including diabetic macular edema (DME). The macular damage is induced by hyperglycemia, which damages vessels supplying blood to the retina and induces hypoxia. The microenvironmental changes stimulate the expression of hypoxia-inducible factors (HIFs), which promote the choroidal endothelial cell transmigration across the retinal pigmented epithelium (RPE) into neurosensory retina, where they proliferate into new vessels under stimulation of the vascular endothelial growth factor (VEGF). In the present study, we have investigated whether PACAP and VIP prevent retinal damage by modulating the expression of HIFs, VEGF, and its receptors. In accord to our hypothesis, we have shown that both peptides are able to significantly reduce HIF-1α and increase HIF-3α expression in ARPE-19 cells exposed to hyperglycemic/hypoxic insult. This effect is also related to a reduction of VEGF and its receptors expression. Moreover, both peptides also reduce the activation of p38 mitogen-activated protein kinase (MAPK), a pro-apoptotic signaling pathway, which is activated by VEGFR-1 and 2 receptors. In conclusion, our study has further elucidated the protective role performed by PACAP and VIP, against the harmful combined effect of hyperglycemia/hypoxia characterizing the DME microenvironment. J. Cell. Physiol. 232: 1209-1215, 2017. © 2016 Wiley Periodicals, Inc.

Light‐induced oxidative stress production in the rod outer segments

PurposeOxidative stress is involved in retinal diseases such as diabetic retinopathy, age‐related macular degeneration and retinal damage by light, characterized by Reactive Oxygen Intermediates (ROI) production. Rod Outer Segments (OS), display a mitochondria‐like activity, producing ATP and consuming oxygen through the expression of the electron transfer chain (ETC) complexes I–IV and F1Fo‐ATP synthase. As the ETC is a major source of ROI generation, here we investigated the ultimate ROI source in the OS after blue light (BL) or ambient light irradiation.MethodsSamples were: purified bovine OS and organotypic model of photoreceptors (from C57BL/6 mice) irradiated with BL (peak, 405 nm). Histochemical assays were conducted on unfixed eye culture sections. To test ROI, 5‐(and‐6)‐chloromethyl‐2′,7′‐dichlorodihydrofluorescein diacetate was used both for cyofluorimentric assay in purified OS and for live staining of retinas explanted from eye cultures. Oxidative metabolism was investigated by ATP synthesis and oximetry in purified OS. Malondialdehyd (MDA) concentration in OS homogenates was evaluated.ResultsUnder BL stress, ROI and MDA production increased while O2 consumption and ATP synthesis were impaired in OS after 6 h BL treatment. Impairment of respiratory Complexes I and II after BL exposure, both in the OS and IS was found. In ambient light, purifed OS, even in the absence of respiring substrates, produced a consistent amount of ROI, while in the dark, OS ATP synthesis is negligible.ConclusionsLikely, severe malfunctioning of OS aerobic respiratory capacity after BL treatment is secondary to a self‐induced damage after initial over‐functioning of both phototransduction and respiratory chain, with ROI production. Correlation among ROI production and phototransduction activity as well as possible antioxidant supplementation are discussed.

Using optical coherence tomography to evaluate macular changes after surgical management for rhegmatogenous retinal detachment

Incomplete visual recovery, color vision defects, or persistent metamorphopsia may persist even after successful surgery for rhegmatogenous retinal detachment (RRD), especially in cases of RD with macula off, suggesting microstructural macular damage that standard fundus biomicroscopy could not detect. We compared spectral-domain optical coherence tomography imaging with preoperative and postoperative visual acuity to evaluate the relationship between morphological changes in the outer retina and visual outcome after successful repair of RRD with macula on or off. We enrolled 43 patients (43 eyes) with successful repair of RRD and a minimum 6-month follow up after surgery in this retrospective research. Patients accepted spectral-domain optical coherence tomography postoperatively and visual acuity examination preoperatively and postoperatively. The mean age of the patients was 48.74 ± 12.68 years (range: 16–77 years). The mean visual acuity (logarithm of minimal angle of resolution) before surgery was 0.87 ± 0.70. Disrupted ellipsoid zone was noted in one of 11 eyes in the macula-on group (9.1%) and 19 of 32 eyes in the macula-off group (59.4%). Disrupted external limiting membrane (ELM) was noted in no eye in the macula-on group (0%) and 11 of 32 eyes in the macula-off group (34.4%). The macula-off group was associated with better postoperative visual gains than the macula-on group (p = 0.013). Patients with integrity of the ellipsoid zone and ELM were associated with significant visual improvement than patients with disruption of the ellipsoid zone or ELM.

The 24-2 Visual Field Test Misses Central Macular Damage Confirmed by the 10-2 Visual Field Test and Optical Coherence Tomography.

PurposeTo determine the extent to which the 24-2 visual field (VF) misses macular damage confirmed with both 10-2 VF and optical coherence tomography (OCT) tests and to evaluate the patterns of damage missed.MethodsOne hundred forty-one eyes of 141 glaucoma patients or suspects underwent 24-2 VF (mean deviation [MD] better than −6 dB), 10-2 VF, and OCT testing. Retinal nerve fiber layer (RNFL) and retinal ganglion cell plus inner plexiform (RGC+) probability plots were combined with 10-2 VF probability plots. Eyes were classified as “abnormal macula” if abnormal regions on both the 10-2 VF and OCT plots agreed. The number of abnormal eyes missed (i.e., false negatives) was determined for the following 24-2 VF metrics: MD; pattern standard deviation (PSD); glaucoma hemifield test (GHT); cluster criteria (CC); and abnormal points within ± 10°. Eyes that were missed on one or more of the 24-2 metrics were classified by damage type based upon circumpapillary RNFL thickness plots.ResultsFifty-nine (41.8%) eyes were classified as “abnormal macula,” and comprised the reference standard. Of the 59, 31 (52.5%) were missed by one or more of the 24-2 metrics. The individual 24-2 metrics missed between 7 (CC) and 20 (MD) eyes. The eyes missed had widespread macular damage, as well as both shallow and deep local defects.ConclusionsEyes with macular glaucomatous damage may be classified as normal based on the 24-2 VF alone.Translational RelevanceTo detect macular damage with perimetry, the 10-2 VF test (or a modified 24-2 VF test) is essential.

Asymmetric Macular Structural Damage Is Associated With Relative Afferent Pupillary Defects in Patients With Glaucoma.

PurposeWe examined the relationship between relative afferent pupillary defects (RAPDs) and macular structural damage measured by macular thickness and macular ganglion cell-inner plexiform layer (mGCIPL) thickness in patients with glaucoma.MethodsA cross-sectional study was done of 106 glaucoma patients and 85 healthy individuals from the Diagnostic Innovations in Glaucoma Study. All subjects underwent standard automated perimetry (SAP) and optic nerve and macular imaging using Cirrus Spectral Domain Optical Coherence Tomography (SDOCT). Glaucoma was defined as repeatable abnormal SAP or progressive glaucomatous changes on stereo photographs. Pupil responses were assessed using an automated pupillometer, which records the magnitude of RAPD (RAPD score), with additional RAPD scores recorded for each of a series of colored stimuli (blue, red, green, and yellow). The relationship between RAPD score and intereye differences (right minus left eye) in circumpapillary retinal nerve fiber layer (cpRNFL) thickness, mGCIPL, macular thickness, and SAP mean deviation (MD), was examined using linear regression.ResultsThere was fair correlation between RAPD score and asymmetric macular structural damage measured by intereye difference in mGCIPL thickness (R2 = 0.285, P < 0.001). The relationship between RAPD score and intereye difference in macular thickness was weaker (R2 = 0.167, P < 0.001). Intereye difference in cpRNFL thickness (R2 = 0.350, P < 0.001) and SAP MD (R2 = 0.594, P < 0.001) had stronger association with RAPD scores compared to intereye difference in mGCIPL and macular thickness.ConclusionsObjective assessment of pupillary responses using a pupillometer was associated with asymmetric macular structural damage in patients with glaucoma.

Macular Retinal Nerve Fiber Layer Axonal Damage and Macular Retinal Ganglion Cell Loss in Clinically Isolated Syndrome: A Potential Marker of Neurodegeneration? (P4.265)

Macular Retinal Nerve Fiber Layer Axonal Damage and Macular Retinal Ganglion Cell Loss in Clinically Isolated Syndrome: A Potential Marker of Neurodegeneration? (P4.265)

Central Glaucomatous Damage of the Macula Can Be Overlooked by Conventional OCT Retinal Nerve Fiber Layer Thickness Analyses.

To assess the extent to which glaucomatous damage of the macula can be detected using the summary statistics of a commercial report based upon the circumpapillary retinal nerve fiber layer (cpRNFL) thickness obtained with frequency domain optical coherence tomography (fdOCT). One hundred forty-three eyes of 143 open-angle glaucoma patients and suspects (56.4 ± 13.8 years) had 10-2 visual fields (VFs) and fdOCT macular and disc cube scans. RNFL and retinal ganglion cell plus inner plexiform layer thickness and probability maps were generated and combined with 10-2 VF information in a single-page, custom report previously described. Three graders evaluated these reports and classified each eye as "abnormal macula" or "normal macula." Commercially available fdOCT reports for cpRNFL thickness were generated using the automatic segmentation algorithm and norms from the machine. The ability of the reports to detect macular damage was analyzed in three ways: temporal quadrant (TQ) < 5%; TQ < 5% or clock hour 7 < 1% (TQ + CH7); and clock hours 7 through 10 with two sectors < 5% or one sector < 1% (CH7-10). Sixty-one (43%) eyes were classified "abnormal macula" and 41 (29%) as "normal macula"; the 10-2 VFs and OCT probability maps did not agree in the remaining eyes. Of the 61 abnormal eyes, the TQ criterion missed 47 (77%); TQ + CH7 missed 24 (39%); and CH7-10 missed 22 (36%). Conventional cpRNFL analyses on commercial OCT reports can miss macular (central field) damage. To detect glaucomatous damage of the macula, additional tests, such as macular cube scans and/or 10-2 VFs, should be performed.

Correlation between radiation dose and damage to optic disc and macula in eyes treated with ruthenium brachytherapy

PurposePoor visual acuity and blindness due to retinal damage are challenging side effects to 106Ru‐plaque treatments of malignant melanomas. In this study, we evaluated the dose to fovea and to the optic nerve and investigated the link between dose and the occurrence of macular and optic nerve damage.MethodsThe study included 54 patients treated in 2005 and 2006 in Copenhagen University Hospital, Denmark. Six patients were excluded due to missing information on ocular outcome. Using dedicated commercial software, the tumour was retrospectively contoured on pre‐treatment fundus images. The position of the plaque was determined from the radiation scar in post‐treatment fundus images and enabled to recreate the dose distribution. The presence of ocular damage was determined from the same post‐treatment fundus images. The dose to the fovea and optic nerve were reported and compared to the presence of ocular damage.ResultsThe estimated dose to the macula for patients with macular damage (median: 64 Gy, range: 7–668 Gy) was significantly larger than for patients with no macular damage (me‐ dian: 7, range: 0‐31 Gy) (p = 1.8·10−7). Optic nerve doses for patients with optic nerve damage (median: 87 Gy, range: 38–257 Gy) similarly differed significantly from those for patients without damage (median: 17 Gy, range: 0–122 Gy) (p = 1.7·10−4).ConclusionsAfter 106Ru‐plaque treatment, patients where ocular damage was identified had received a significantly higher dose to the macula and optic nerve compared to patients with no signs of ocular damage.

Cell penetrating peptide constructs: A novel drug delivery to the eye

PurposeIn neovascular age‐related macular degeneration (AMD) blood vessels grow from the choroid under the retina causing macular damage and scarring. Anti‐VEGF drugs such as, ranibizumab or aflibercept are administered by intravitreal injection to treat AMD related neovascularisation, We present a novel cell‐penetrating peptide construct (CPPC) topical delivery system to deliver Ranibizumab to the retina using drops.MethodsPeptides were produced using standard solid‐phase peptide synthesis. They were analysed using mass spectrometry and purified using high‐pressure liquid chromatography and used at a purity of &gt;95%. CPPC were built around the drugs by vortexing for 10 seconds and incubating at room temperature. Drug delivery experiments were carried out ex‐vivo in freshly enucleated porcine eyes. In vivo experiments were carried out in C57 mice. Mice had a three 100 μm laser burns to the choroid to model neo‐vascularisation in AMD. They then received a single intravitreal injection of an anti‐VEGF agent or CPPC/Ranibizumab applied topically to the conjunctival sac twice daily for the duration of the experiment. Choroidal neovascularisation was measured by immunohistochemistry.ResultsEx vivo delivery to enucleated porcine eyes demonstrated that a single 60 μL drop could deliver 1.7 ± 0.4 μg/mL of ranibizumab to the vitreous cavity. Confocal images of immunohistochemistry on retinal wholemounts showed ranibizumab within the retina. In vivo experiments demonstrated both intravitreal injection and CPPC bound Ranibizumab reduced neovascularisation equally, compared to controlsConclusionsCPPC can be used topically to deliver therapeutic levels of Ranibizumab to the posterior segment.

Parainflammation, chronic inflammation, and age-related macular degeneration.

Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration.

Choosing two points to add to the 24-2 pattern to better describe macular visual field damage due to glaucoma.

A recent study has shown that the paracentral upper visual field in the macular region is often affected in glaucoma and suggested that two test locations within the central 10° should be added to the Humphrey 24-2 visual field test pattern to detect such damage. This study employed data collected using a different visual field test pattern to determine whether the same two-test locations are supported as the most informative regarding visual field loss. A data set of 62 patients with glaucoma and 48 controls had visual field assessments on the Medmont perimeter M700 (Central Threshold or Glaucoma test). Twelve 24-2 locations within central 10° of visual field were derived by interpolation of the nearest neighbours of the Medmont data. The remaining 24 Medmont locations in the central 10° of the glaucomatous set were labelled as abnormal if their thresholds fell outside the lower 5th centile of the age-corrected values for the same location from the control group. All possible pairs of the 24 locations were then assessed for diagnostic power by counting the number of patients that had 0, 1 or 2 abnormal locations in a pair. Overwhelmingly, pairs of locations in the superior macular region were more often abnormal than pairs in the inferior. About 50 pairs of locations had equivalent ability to detect damage, with the best pair having 74% of patients with at least one of the locations as abnormal, and 52% both. Adding a pair of locations to the superior macular region of the Humphrey Visual Field 24-2 pattern increases the number of abnormal locations identified in individuals with glaucoma.

Myopic foveoschisis: a clinical review.

To review the literature on epidemiology, clinical features, diagnostic imaging, natural history, management, therapeutic approaches, and prognosis of myopic foveoschisis. A systematic Pubmed search was conducted using search terms: myopia, myopic, staphyloma, foveoschisis, and myopic foveoschisis. The evidence base for each section was organised and reviewed. Where possible an authors' interpretation or conclusion is provided for each section. The term myopic foveoschisis was first coined in 1999. It is associated with posterior staphyloma in high myopia, and is often asymptomatic initially but progresses slowly, leading to loss of central vision from foveal detachment or macular hole formation. Optical coherence tomography is used to diagnose the splitting of the neural retina into a thicker inner layer and a thinner outer layer, but compound variants of the splits have been identified. Vitrectomy with an internal limiting membrane peel and gas tamponade is the preferred approach for eyes with vision decline. There has been a surge of new information on myopic foveoschisis. Advances in optical coherence tomography will continually improve our understanding of the pathogenesis of retinal splitting, and the mechanisms that lead to macular damage and visual loss. Currently, there is a good level of consensus that surgical intervention should be considered when there is progressive visual decline from myopic foveoschisis.

Modifying the Conventional Visual Field Test Pattern to Improve the Detection of Early Glaucomatous Defects in the Central 10°

To simulate modified versions of the 24-2 (6° grid) visual field (VF) test pattern by adding points from the 10-2 (2° grid) test pattern, and to assess their ability to detect early glaucomatous defects in the central 10°. One hundred forty-four eyes of 144 glaucoma patients and suspects with 24-2 mean deviations better than -6 dB were tested with 10-2 and 24-2 VFs. Based upon both 10-2 VF and optical coherence tomography probability plots, 63 hemifields were defined as abnormal, while 121 hemifields were defined as normal. Three modified 24-2 VF test patterns, called 24-2 +4, 24-2 +16 (Even), and 24-2 +16 (Empirical), were simulated by adding 4 or 16 test points from the 10-2 VF. Based upon the number of abnormal points (P ≤ 5%), the area under the ROC curves (AROC scores) of the three modified 24-2 VFs were significantly greater than that of the 24-2 VF for both the upper and lower VF. For a specificity of 85%, the number of true positives was 25 (24-2), 30 (24-2 +4), 31 (24-2 +16, even), and 32 (24-2 +16, empirical) of 34 total true positives for the upper VF and 23, 26, 27, and 28 of 29 for the lower VF. Adding points from the 10-2 test pattern to the 24-2 test pattern significantly improved its ability to detect macular defects without employing more test points than a single 10-2 test. Additional central points should be added to the 24-2 pattern to improve the detection of macular damage.

Safety of transfoveal subthreshold diode micropulse laser for fovea-involving diabetic macular edema in eyes with good visual acuity.

To determine the safety of transfoveal subthreshold diode micropulse laser for fovea-involving diabetic macular edema. The records of all patients treated with transfoveal subthreshold diode micropulse laser for fovea-involving diabetic macular edema in two retina clinics were reviewed. The eligibility included fovea-involving diabetic macular edema by spectral domain optical coherence tomography and pretreatment visual acuity of 20/40 or better. Thirty-nine eyes of 27 patients aged 50 years to 87 years (mean, 69 years) were included. Postoperative follow-up ranged from 3 months to 36 months (mean, 11 months). Fourteen patients were insulin dependent, and 19 had nonproliferative retinopathy. The preoperative visual acuity was 20/20 (10 eyes), 20/25 (10 eyes), 20/30 (8 eyes), and 20/40 (11 eyes). No eye had evidence of laser-induced macular damage by any imaging means postoperatively. There were no adverse treatment effects. Logarithm of the minimum angle of resolution visual acuity was improved on average of 0.03 units at 4 months to 7 months of follow-up (P = 0.0449, paired t-test) and otherwise stable. The central foveal thickness was improved at 4 months to 7 months (P = 0.05, paired t-test) and 8 months to 12 months, postoperatively (P = 0.04, mixed model accounting). Maximum macular thickness was improved at 4 months to 7 months postoperatively (P = 0.01, paired t-test and mixed model accounting). In a small retrospective series, transfoveal subthreshold diode micropulse laser was safe and effective for the treatment of fovea-involving diabetic macular edema in eyes with good preoperative visual acuity that were not the candidates for conventional photocoagulation or intravitreal injection. Further study is warranted.

Clinicopathological Findings in Abusive Head Trauma: Analysis of 110 Infant Autopsy Eyes

To investigate the histopathology in a large series of autopsy eyes from children with abusive head trauma. Retrospective case-control series. One hundred and ten eyes from 55 autopsies examined at an academic tertiary referral center over 21 years were tabulated for histopathology: subdural hemorrhage in the optic nerve sheath, intrascleral hemorrhage, any retinal hemorrhage, ora-extended hemorrhage, cherry hemorrhage, perimacular ridge, and internal limiting membrane tear. Select tissues with cherry hemorrhage were further examined by transmission electron microscopy. Sixty eyes were identified as "abusive head trauma" (cases), 46 as "alternative cause" (controls), and 4 as "abusive head trauma survivor". Cases were legally verified or confirmed by confession in all except 1 case. All ocular histopathologic observations from cases were similar or more frequent in infants younger than 16 months of age. When present, a cherry hemorrhage and perimacular ridge were most often found together, and only with a torn internal limiting membrane. Both abusive head trauma survivor cases demonstrated severe optic nerve atrophy and macular ganglion cell loss. Younger infants may be even more susceptible to damage from vitreomacular traction by rotational and/or acceleration-deceleration forces. Identifying cherry hemorrhages may aid abusive head trauma diagnosis. Survivor abusive head trauma pathology demonstrates unique, irreversible macular and optic nerve damage.

Severity-dependent association between ganglion cell inner plexiform layer thickness and macular mean sensitivity in open-angle glaucoma.

To evaluate the structure-function relationship between macular mean sensitivity (mMS) and ganglion cell inner plexiform layer thickness (GCIPLT) according to glaucoma severity and to compare it with that between mMS and peripapillary retinal nerve fibre layer thickness (pRNFLT), using spectral-domain (Cirrus) optical coherence tomography (OCT). Three hundred and sixty-two eyes of 362 patients with open-angle glaucoma of differing severity (preperimetric, early, moderate, and advanced) together with 130 eyes of 130 healthy controls, all of whom underwent Cirrus OCT imaging and 30-2 standard automated perimetry (SAP), were included in the study. The mMS was assessed by calculating the average of sensitivities at 12 central SAP points. The relationships between mMS and the various GCIPLT (average, minimum, superior, and inferior) parameters obtained by Cirrus OCT were evaluated according to disease severity using a linear regression model and were then compared with those between pRNFLT parameters and mMS. The mMS and GCIPLT showed stronger relationships with the increase in glaucoma severity, but this was not the case with the pRNFLT parameters. In preperimetric glaucoma, the associations between mMS and both GCIPLT and pRNFLT were not significant. In moderate and advanced glaucoma, all GCIPLT parameters showed a statistically significant relationship with mMS. However, pRNFLT showed a moderate association in early and moderate glaucoma and none at all in advanced glaucoma. GCIPLT showed a stronger structure-function relationship with mMS in more advanced stages of glaucoma compared to pRNFLT. GCIPLT reflected macular functional damage better than pRNFLT in advanced glaucoma.

Prevalence and Nature of Early Glaucomatous Defects in the Central 10° of the Visual Field

The macula is essential for visual functioning and is known to be affected even in early glaucoma. However, little is currently understood about the prevalence and nature of central vision loss in early glaucoma. To determine the prevalence and characteristics of visual field (VF) defects in the central 10° in glaucoma suspects and patients with mild glaucoma using a prospective design. This prospective observational cohort study was conducted at an outpatient glaucoma specialty clinic. One hundred eyes from 74 patients with glaucomatous optic neuropathy and a 24-2 VF with mean deviation better than -6 dB were prospectively studied and tested with a 10-2 test. Reliable: VF hemifields were classified as abnormal based on a cluster criterion, and abnormal 10-2 VFs were categorized based on the pattern of abnormal points: arcuatelike, widespread, or other. In addition, at each point of the 10-2 VF, the total deviation values were averaged across eyes and the number of abnormal points with total deviation values below a specific criterion level were calculated. RESULTS There appeared to be as many abnormal 10-2 hemifields (53%) as abnormal 24-2 hemifields (59%). Of the eyes with normal 24-2 hemifields, 16% were classified as abnormal when the 10-2 test was used. Of the abnormal 10-2 hemifields, 68%, 8%, and 25% were arcuatelike, widespread, and other, respectively. The average total deviation values and number of abnormal points plots revealed superior VF defects that were deeper and closer to fixation than those in the inferior VF. The 10-2 VF was abnormal in nearly as many hemifields as was the 24-2 VF, including some with normal 24-2 VF, suggesting that the 24-2 test is not optimal for detecting early damage of the macula. The pattern of the defects was in agreement with a recent model of macular damage.