Neonatal Macular Hemorrhage in a Term Healthy Infant: 18-Year Follow-up.

Unobstructed binocular vision is required during the critical period of vision development to obtain optimal visual acuity in each eye and binocular stereopsis. In this article, we report 18-year follow-up of a full-term, otherwise healthy infant noted to have dense premacular hemorrhage occluding the visual axis in the left eye on retinal imaging performed 48 hours after birth. Serial examinations by the retina service were performed weekly for 10 weeks as the hemorrhage resolved spontaneously. Shortly thereafter, visual acuity revealed fixation was present, but the mother noted intermittent left eye esodeviation. At 90 days of life, the infant was seen by pediatric ophthalmology and started on 1 to 2 hours patching of the right eye daily for the esotropia, which was maintained through 24 months. At 18 years of age, the patient had orthophoria alignment, no spectacle correction, vision of 20/20 in the right eye and 20/25 in the left eye, and normal binocularity and stereopsis. Intermittent esodeviation on the left eye was observed when the patient was fatigued. Early identification of a visual axis occlusion led to prompt referral for the esotropia and initiation of patching therapy. This patient ultimately achieved a very favorable visual functional outcome that may not have been possible without early detection and management. This case report describes the longest-term published follow-up of a neonatal macular hemorrhage. [Ophthalmic Surg Lasers Imaging Retina 2024;55:354-357.].

Influence of submacular hemorrhage at baseline on the long-term outcomes of aflibercept treatment for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To investigate the influence of submacular hemorrhage (SMH) at baseline on long-term visual outcomes of patients with typical age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept (IVA). METHODS: In this retrospective study, eyes of treatment-naïve patients with tAMD and PCV who initiated IVA under a treat-and-extend regimen and were followed up for ≥ 5 years were classified into the tAMD-SMH ( +), tAMD-SMH (-), PCV-SMH ( +), and PCV-SMH (-) groups based on the presence of SMH at baseline. Best-corrected visual acuity (BCVA) changes and macular fibrosis and atrophy incidences were assessed. RESULTS: This study included 127 eyes (127 patients), including 51 with tAMD and 76 with PCV; 18 eyes had SMH at baseline. In the tAMD-SMH ( +) group (n = 6), the mean logMAR BCVA significantly deteriorated from 0.59 ± 0.45 at baseline to 0.88 ± 0.47 at the final visit (P = 0.024). No significant BCVA changes were observed in the tAMD-SMH (-) (n = 45), PCV-SMH ( +) (n = 12), or PCV-SMH (-) (n = 64) groups (all P > 0.05). The tAMD-SMH ( +) group showed a significantly higher incidence of macular fibrosis at the final visit than did the tAMD-SMH (-) group (P = 0.042). There was no influence of baseline SMH on the macular fibrosis incidence in eyes with PCV and the macular atrophy incidence in eyes with tAMD and PCV. CONCLUSION: The presence of SMH at baseline resulted in poorer long-term visual acuity in eyes with tAMD, even with aflibercept treatment. However, no such influence was observed in eyes with PCV.

VITRECTOMY WITH SUBRETINAL INJECTION OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR FOR SUBMACULAR HEMORRHAGE WITH OR WITHOUT VITREOUS HEMORRHAGE.

PURPOSE: To evaluate the outcomes and prognostic factors of pars plana vitrectomy combined with subretinal injection of recombinant tissue plasminogen activator for submacular hemorrhage (SMH) patients with or without vitreous hemorrhage (VH). METHODS: Sixty-four eyes of 64 patients with SMH underwent pars plana vitrectomy with subretinal injection of recombinant tissue plasminogen activator. Best-corrected visual acuity, SMH displacement, and postoperative complications were analyzed. Predictive factors of the final best-corrected visual acuity were determined using multivariant linear regression. RESULTS: There were 26 eyes with VH and 38 eyes without VH best-corrected visual acuity significantly improved in both VH group (from 2.27 ± 0.40 to 1.25 ± 0.70 logarithm of the minimum angle of resolution) and non-VH group (from 1.76 ± 0.55 to 0.85 ± 0.65 logarithm of the minimum angle of resolution). Complete displacement of SMHs was observed in 47 (73.43%) eyes. Postoperative complications included recurrent SMH (4.69%), recurrent VH (10.94%), rhegmatogenous retinal detachment (3.13%), and epiretinal membrane (4.68%). Treatment-naive condition, early surgery, and younger age were significantly associated with better final best-corrected visual acuity ( B = 0.502, 0.303, and 0.021, respectively, with all P < 0.05). CONCLUSION: Pars plana vitrectomy combined with subretinal recombinant tissue plasminogen activator injection is an effective treatment for SMH patients with and without VH.

Clinical Significance of Optic Disc Hemorrhage Size in Visual Field Progression in Glaucoma.

PURPOSE: To investigate the correlation between optic disc hemorrhage (DH) size and glaucoma progression. DESIGN: A retrospective observational cohort study METHODS:   SETTING: A single tertiary hospital in South Korea STUDY POPULATION: Two hundred and fifty (250) open-angle glaucoma (OAG) patients with DH. Participants were followed for 5 years or longer, with a minimum of 5 visual field (VF) tests. OBSERVATION PROCEDURE: The DH area was calculated by comparing the pixel numbers of the DH area with the disc area based on optical coherence tomography (OCT). For recurrent DH cases, we calculated the average DH area. DH size was classified as large or small based on the median value. Rates of mean deviation (MD) loss were determined using guided progression analysis (GPA). Univariable and multivariable regression analyses were performed to identify significant predictors of MD loss. MAIN OUTCOME MEASURES: DH size and longitudinal VF progression RESULTS: The mean follow-up period was 11.1 ± 3.6 years. The group with large DH showed faster global MD loss relative to the group with small DH (-0.51±0.48 dB/y vs -0.36 ± 0.42 dB/y, P = .01). In the multivariable model, mean DH size, maximum DH size, and initial MD were all significantly associated with the overall rate of MD loss (all P < .05). CONCLUSIONS: DH size was associated with the rate of VF deterioration. Eyes with larger DH showed more pronounced VF progression.

RELATIONSHIP BETWEEN RETINAL HEMORRHAGE ON GREEN AND RED CHANNELS OF ULTRA-WIDEFIELD FUNDUS IMAGES AND RETINAL PERFUSION IN ACUTE BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To explore the relationship between retinal hemorrhage in the green and red channels on ultra-widefield fundus images and the nonperfusion area (NPA) on ultra-widefield fundus fluorescein angiography in patients with acute branch retinal vein occlusion (BRVO). METHODS: This was a retrospective cross-sectional study with 96 patients, including 46 with ischemic BRVO and 50 with nonischemic BRVO. Correlation analysis between green channel hemorrhage (GCH), red channel hemorrhage (RCH), and NPA was performed. Panretina was divided into posterior and peripheral areas. RESULTS: Ischemic BRVO showed significantly higher GCH% and RCH% than nonischemic BRVO in the peripheral regions (both P < 0.001), whereas no significant differences were observed in the panretinal and posterior areas (all P > 0.05). Significant correlations were found between NPA% in the panretinal and peripheral areas and the corresponding GCH% and RCH% (all P < 0.01). However, no significant correlation was observed between posterior NPA% and posterior GCH% or RCH% (both P > 0.05). In addition, peripheral GCH% and RCH% were related to panretinal NPA% (r = 0.506, P < 0.001; r = 0.558, P < 0.001). CONCLUSION: Retinal hemorrhage on ultra-widefield fundus image was significantly associated with NPA, providing insights for assessing retinal perfusion status in acute BRVO patients.

What Is Left After Resolution of Neonatal Retinal Hemorrhage: The Longitudinal Long-term Outcome in Foveal Structure and Visual Function.

PURPOSE: Neonatal retinal hemorrhage (NRH) is one of the most common neonatal fundus conditions. Hemorrhage resolves spontaneously; however, its long-term outcome is unknown yet. The current study explores the long-term role of NRH in foveal structure and visual function. DESIGN: Cohort study (a prospective longitudinal study, in which the participants were followed up for 4-6 years). METHODS: A total of 125 healthy newborns during 2013-2015, including 50 newborns with NRH and 75 newborns without NRH, were enrolled. The eyes with NRH were further categorized into the foveal hemorrhage (FH) group and non-FH group. A comprehensive ophthalmic examination including best-corrected visual acuity (BCVA) measurement, slit-lamp examination, refractive error measurement, scanning laser ophthalmoscopy, and spectral-domain OCT was performed. Total retinal thickness (TRT) and the inner and outer retinal layers in the fovea were measured and compared. RESULTS: The NRH was absorbed within 2.1 ± 0.98 weeks (median: 3 weeks). No difference was noted in the demographic characteristics between the groups; there was no significant difference in the logMAR BCVA (P = .83) or in the TRT. Subgroup analysis showed that TRT at the fovea in the FH group was significantly thicker (P = .005). Segmentation analysis showed a significantly thicker foveal outer nuclear layer (ONL) in the FH group (P = .017). CONCLUSIONS: Birth-related retinal hemorrhage, even FH, might not lead to obvious visual abnormalities at the age of 4 years, at least according to this study with relatively small sample size. However, a thicker fovea, mainly attributed to a wider ONL and a shallower foveal pit, is noted in our study.

REVERSIBLE RETINAL TOXICITY IN A PATIENT TAKING AXITINIB.

PURPOSE: Axitinib (Inlyta, New York, NY) is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma after failure of one previous systemic therapy. A case of bilateral retinal hemorrhages and cotton wool spots associated with axitinib is reported. METHODS: A 62-year-old woman with a 4-year history of renal cell carcinoma with metastases was treated with axitinib at a maximum oral daily dose of 8 mg. Soon after beginning higher dose therapy, she developed blurred vision, floaters, and photopsias. RESULTS: Funduscopic examination of both eyes revealed cotton wool spots and retinal hemorrhages that improved with cessation of therapy. CONCLUSION: Axitinib may be associated with microangiopathic retinal toxicity.

RESPONSE TO INTRAVITREAL AFLIBERCEPT IN A PATIENT WITH PERIPHERAL EXUDATIVE HEMORRHAGIC CHORIORETINOPATHY.

PURPOSE: To draw attention to a novel treatment agent for vision loss associated with peripheral exudative hemorrhagic chorioretinopathy. METHODS: The case of an 83-year-old man suffering with loss of left visual acuity vision in the context of vitreous hemorrhage secondary to peripheral exudative hemorrhagic chorioretinopathy is described. RESULTS: Resolution of vitreous hemorrhage and subretinal hemorrhage was demonstrated after treatment with aflibercept. CONCLUSION: Peripheral exudative hemorrhagic chorioretinopathy is discussed in terms of its presentation, pathophysiology, and existing treatment methodologies.

Determining the Tractional Forces on Vitreoretinal Interface Using a Computer Simulation Model in Abusive Head Trauma.

PURPOSE: Abusive head trauma (AHT) is the leading cause of infant death and long-term morbidity from injury. The ocular consequences of AHT are controversial, and the pathophysiology of retinal research findings is still not clearly understood. It has been postulated that vitreoretinal traction plays a major role in the retinal findings. A computer simulation model was developed to evaluate the vitreoretinal traction and determine whether the distribution of forces in different layers and locations of the retina can explain the patterns of retinal hemorrhage (RH) seen in AHT. DESIGN: Computer simulation model study. METHODS: A computer simulation model of the pediatric eye was developed to evaluate preretinal, intraretinal, and subretinal stresses during repetitive shaking. This model was also used to examine the forces applied to various segments along blood vessels. RESULTS: Calculated stress values from the computer simulation ranged from 3-16 kPa at the vitreoretinal interface through a cycle of shaking. Maximal stress was observed at the periphery of the retina, corresponding to areas of multiple vessel bifurcations, followed by the posterior pole of the retina. Stress values were similar throughout all 3 layers of the retina (preretinal, intraretinal, and subretinal layers). CONCLUSIONS: Ocular manifestations from AHT revealed unique retinal characteristics. The model predicted stress patterns consistent with the diffuse retinal hemorrhages (RH) typically found in the posterior pole and around the peripheral retina in AHT. This computer model demonstrated that similar stress forces were produced in different layers of the retina, consistent with the finding that retinal hemorrhages are often found in multiple layers of the retina. These data can help explain the RH patterns commonly found in AHT.

Ocular Complications of Checkpoint Inhibitors and Immunotherapeutic Agents: A Case Series.

Background: Ophthalmologists have a role in assessing immune-related adverse events (IRAE) in oncology patients on immunotherapy. We assessed the utility of a hospital-wide toxicity team in referring patients with new ocular symptoms for examination. We also identified new immunotherapy agents causing ocular side-effects.Design: A cohort study of eight consecutive patients on immunotherapy, who developed ocular IRAE from November 1, 2017 to June 30, 2019. All were seen at the Ocular Immunology Division of the Wilmer Eye Institute and referred by the Johns Hopkins Toxicity Team.Results: All eight patients on had IRAEs; were treated with corticosteroid drops or observation with clinical resolution. Two new agents, epocadostat and daratumumab, were associated with the development of uveitis.Conclusion: Ophthalmologists play an important role in a hospital-wide toxicity team and need to include IRAEs in their differential diagnosis. Given new drug development, ophthalmologists may be the first to identify IRAEs.

Optic disc hemorrhage in nonglaucomatous eyes: A cross-sectional study with average 8-year follow-up.

PURPOSE: To characterize changes in the retinal nerve fiber layer (RNFL) and peripapillary vessel density (VD) at the site of disc hemorrhage (DH) in nonglaucomatous eyes. MATERIALS AND METHODS: This retrospective cross-sectional study included nonglaucomatous eyes diagnosed with unilateral DH. The change of DH was recorded using disc photography. Both anatomical data and functional visual field (VF) data were collected using optical coherence tomography angiography and Humphrey VF examination. RESULTS: Sixteen patients were included with average follow-up duration of 95 months. Almost half of DH episodes was initially presented at the inferotemporal area of the optic disc. Pigment formation at the previous DH site after resolution was noted in 12.5% of eyes. Sectoral radial peripapillary VD at the DH site was significantly lower in DH eyes than in the control group; however, the sectoral RNFL thickness at the DH site was not significantly decreased. Progression of the VF defect corresponding to the DH site was found in 81.3% of eyes despite regular use of antiglaucoma agents. The mean change in the VF mean deviation was -0.64 dB/year in DH eyes. CONCLUSION: During long follow-up periods, decreased peripapillary VD at the DH site and progression of the VF defect corresponding to the DH site were detected in nonglaucomatous eyes. Retinal pigmentation with an RNFL defect is a clue for DH, although RNFL showed no significant change. Antiglaucoma treatment may not prevent the deterioration of visual function.

Spontaneous Resolution of Foveal Sub-internal Limiting Membrane Hemorrhage with Excellent Visual and Anatomical Outcome in a Patient with Acute Myeloid Leukemia.

Sub-internal limiting membrane (sub-ILM) hemorrhage is a distinct type of retinal hemorrhage in which the blood accumulates between ILM and nerve fiber layer. Little is known about visual prognosis as well as ideal management of foveal sub-ILM hemorrhage in patients with acute leukemia. Herein, we presented a case of acute myeloid leukemia with foveal sub-ILM hemorrhage. Observation alone resulted in complete resolution of hemorrhage with good visual and anatomical outcome.

Densitometric Profiles of Optic Disc Hemorrhages in the Ocular Hypertension Treatment Study.

PURPOSE: The origin of blood in glaucoma-related disc hemorrhages (DH) remains unknown. A prior clinic-based study of primary open-angle glaucoma (POAG)-related DH showed that they had grayscale pixel intensities more similar to blood from retinal macroaneurysms and adjacent retinal arterioles than to blood from retinal vein occlusions or adjacent retinal venules, suggesting an arterial source. Here we assessed the densitometric profile of DH from fundus photographs in the Ocular Hypertension Treatment Study (OHTS). DESIGN: Retrospective cross-sectional study of prospectively collected images. METHODS: Stereo disc photographs of 161 DH events from 83 OHTS participants (mean age [standard deviation (SD)]: 65.6 [9.2] years; 46.6% female; 13.0% black race) were imported into ImageJ to measure densitometry differences (adjacent arterioles minus DH [ΔA] or venules minus DH [ΔV]). Their size as percentage of disc area, ratio of length to midpoint width, and location relative to the disc margin were also analyzed. We performed t tests to compare ΔA and ΔV, analysis of variance to compare ΔA and ΔV across DH recurrent events, and multivariable linear regression to identify determinants of ΔA and ΔV. RESULTS: Mean (SD) ΔA and ΔV were -2.2 (8.7) and -11.4 (9.7) pixel intensity units, respectively (P < .001). ΔA and ΔV each did not differ significantly across recurrence of DH (P ≥ .92) or between DH events with and without POAG (P ≥ .26). CONCLUSIONS: OHTS DH had densitometric measurements more similar in magnitude to adjacent arterioles than venules, supporting an arterial origin for DH. Vascular dysregulation may contribute to disc hemorrhage formation in ocular hypertension.

Bilateral and multiple sub-internal limiting membrane hemorrhages in a familial retinal arteriolar tortuosity patient by Valsalva-like mechanism: an observational case report.

BACKGROUND: Bilateral and multiple Valsalva-related sub-internal limiting membrane (ILM) hemorrhages in a familial retinal arteriolar tortuosity (FRAT) patient is rare, and we treated this patient by both observation and Neodymium yttrium aluminum garnet (Nd: YAG) laser membranotomy methods. CASE PRESENTATION: A 13-year-old female student presented with sudden visual loss and central scotoma in both eyes after running 800 m at the school gym. The examination revealed six sub-ILM hemorrhages with the biggest hemorrhage measuring approximately 1.5-disc diameters (DD) in the right eye and two sub-ILM hemorrhages with the biggest one measuring 5.5 DD in the left eye. The patient was diagnosed as having Valsalva retinopathy associated with FRAT. Nd: YAG laser membranotomy was performed at the biggest hemorrhages and the rest hemorrhages were treated with observation in both eyes. The visual acuity recovered to 20/16 in the right eye and 20/20 in the left eye. Epiretinal membrane (ERM) formation was observed in the left eye. CONCLUSIONS: Nd: YAG laser could be considered for treating premacular hemorrhage in FRAT patient especially when a quick vision recovery was needed. This is the first reported case of a FRAT patient suffering from bilateral and multiple Valsalva-related sub-ILM hemorrhages which were treated by both observation and Nd: YAG laser treatment.

Retinal and visual function in infants with non-accidental trauma and retinal hemorrhages.

PURPOSE: To investigate retinal function and visual outcomes in infants with retinal hemorrhages due to non-accidental trauma (NAT). METHODS: This is a retrospective review of full-field or multifocal electroretinogram (ERG) recordings, visual acuity in log minimum angle of resolution (logMAR), clinical status, and neuroimaging. Multifocal ERGs from the central 40° were compared to corresponding fundus imaging. Visual acuity was measured by Teller cards at follow-up. ERGs were compared to controls recorded under anesthesia. RESULTS: Sixteen children met inclusion criteria (14 recorded during the acute phase and 2 during long-term follow-up). During the acute phase, ERGs (n = 4 full field; n = 10 multifocal ERG) showed abnormal amplitude, latency, or both in at least one eye. Ten subjects had significantly reduced responses in both eyes, 3 of which had an ERG dominated by a negative waveform (absent b-wave or P1). The remaining six subjects had responses in one eye that were near normal (≥ 50% of controls). ERGs were sometimes abnormal in local areas without hemorrhage. ERGs could be preserved in local areas adjacent to traumatic retinoschisis. Two subjects with reduced visual acuity had belated ERGs: One had an abnormal macular ERG and the other had a normal macular ERG implying cortical visual impairment. At follow-up, 10 of 14 subjects had significant visual acuity loss (≥ 0.7 age-corrected logMAR); four subjects had mild vision loss (≤ 0.5 age-corrected logMAR). Visual acuity outcome was not reliably associated with the fundus appearance in the acute phase. All subjects with a negative ERG waveform had severe vision loss on follow-up. CONCLUSIONS: Retinal dysfunction was common during the acute phase of NAT. A near normal appearing fundus did not imply normal retinal function, and ERG abnormality did not always predict a poor visual acuity outcome. However, a negative ERG waveform was associated severe visual acuity loss. Potential artifacts of retinal hemorrhages and anesthesia could not fully account for multifocal ERG abnormalities. Retinal function can be preserved in areas adjacent to traumatic retinoschisis.

Intravitreal Recombinant Tissue Plasminogen Activator and Sulphur Hexafluoride Gas for Submacular Haemorrhage Displacement in Age-Related Macular Degeneration: Looking behind the Blood.

PURPOSE: To evaluate the effectiveness of recombinant tissue plasminogen activator (rtPA) and sulphur hexafluoride gas (SF6) intravitreal injection for the displacement of large submacular haemorrhages (SMH) secondary to neovascular age-related macular degeneration and for guiding the selection of additional treatments or observations for choroidal neovascularization (CNV). METHODS: The medical records of consecutive patients with recent-onset, large SMH, treated at Sacro Cuore Hospital from January 2004 to May 2016, were retrospectively analysed. All eyes underwent a 0.05-mL intravitreal injection of 50 µg rtPA, 0.3 mL of 100% SF6, and then face-down positioning. Afterwards, the eyes received additional treatments for CNV or observation, based on the severity and extent of the underlying pathology. The multimodal imaging features revealed after blood displacement were analysed and then correlated to the treatment selected as a second therapeutic option. RESULTS: A total of 96 eyes met the inclusion criteria and was evaluated in this study. SMH was displaced from the fovea in the majority of the eyes (76%), allowing several diagnostic tools to evaluate the underlying macular features. In 19 cases (19.8%) exhibiting severe macular damage, no additional treatment was applied. In the remaining eyes, subsequent treatments included anti-vascular endothelial growth factor injections (44.8%), photodynamic therapy (n = 2), and submacular surgery (35.4%). Statistically significant correlations were found between the macular findings revealed after blood displacement and the additional treatments or observations selected for the underlying disease. The mean follow-up was 35 months. Improvements in visual acuity were statistically significant up to 3 years. CONCLUSION: Intravitreal rtPA and gas injection was found to be effective for the displacement of large SMH, allowing postoperative diagnostic testing, and thus guiding the opportunity to apply further treatments. The addition of subsequent individualized treatments may allow long-term visual gain in selected cases.