Delayed manifestation of proliferative retinopathy associated with chronic myeloid leukemia.

Purpose: This report highlights a rare case of delayed manifestation of proliferative retinopathy associated with chronic myeloid leukemia (CML) during remission. Observations: Case report and review of the literature; In this case report, we outline the delayed manifestation and clinical progression of proliferative retinopathy in a 52-year-old male patient with a history of CML diagnosed in 2001. Initially, the patient presented with a white blood cell count (WBC) of 402,200/µl, and the leukocytosis persisted until 2005. Thereafter, the patient remained in remission for over 15 years without any visual complaints until 2022. At that time, the patient sought medical attention due to a ten-day history of left eye visual impairment, leading to the discovery of peripheral neovascularization in both eyes and vitreous hemorrhage in the left eye during fundus examination. The WBC count at the time of presentation to the Emergency Department was 10,460/µl. The patient was treated with fluorescein angiography guided panretinal photocoagulation to the areas of ischemic retina. Subsequent follow-up after eight months demonstrated regression of neovascularization. Conclusions and Importance: Our findings highlight the occurrence of proliferative retinopathy in the context of CML, uniquely manifesting during remission. This case emphasizes the importance of ophthalmological assessments not only at the time of CML diagnosis but also during subsequent follow-ups, recognizing the potential for delayed presentation of ocular complications.

Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy.

AIM: To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy (DR) and provide a novel strategy to elucidate the pathological mechanism of DR. METHODS: The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy (PDR), 23 with non-proliferative retinopathy (NPDR), 27 without retinopathy (DM), and 29 from the sex-, age- and BMI- matched healthy controls (29 HC) were analyzed by 16S rDNA gene sequencing. Sixty fecal samples from PDR, DM, and HC groups were assayed by untargeted metabolomics. Fecal metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) analysis. Associations between gut microbiota and fecal metabolites were analyzed. RESULTS: A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR, and the close correlation of the disease progression with PDR-related microbiome and metabolites were found. To be specific, the structure of gut microbiota differed in four groups. Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups, than those in DM and HC groups. A cluster of microbiome enriched in PDR group, including Pseudomonas, Ruminococcaceae-UCG-002, Ruminococcaceae-UCG-005, Christensenellaceae-R-7, was observed. Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group. Arginine, serine, ornithine, and arachidonic acid were significantly enriched in PDR group, while proline was enriched in HC group. Functional analysis illustrated that arginine biosynthesis, lysine degradation, histidine catabolism, central carbon catabolism in cancer, D-arginine and D-ornithine catabolism were elevated in PDR group. Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine, ornithine levels in fecal samples. CONCLUSION: This study elaborates the different microbiota structure in the gut from four groups. The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR. Amino acid and fatty acid catabolism is especially disordered in PDR group. This may help provide a novel diagnostic parameter for DR, especially PDR.

Is vitamin D deficiency associated with retinopathy in type 2 diabetes mellitus? A case-control study.

BACKGROUND AND AIMS: This study aimed to determine the associations between vitamin D deficiency and diabetic retinopathy (DR) progression risk in type 2 diabetes mellitus (T2DM) patients. METHODS: This is a case-control study that enrolled 201 diabetic retinopathy (DR) patients as case and 201 T2DM without DR as a control. Demographic variables were obtained during an interview using a questionnaire, furthermore, anthropometric measures were evaluated based on the standard protocol. In addition, biochemical indices including 25-hydroxyvitamin D, fasting blood glucose (FBG), insulin, Glycosylated hemoglobin (HbA1c), total cholesterol (TC), LDL-C, HDL-C, and triglyceride (TG) were assessed for all of the participants. Multivariate logistic regression was performed to estimate the relationship between vitamin D and retinopathy. RESULTS: Based on the statistical analysis of age, sex, and BMI there was no significant difference between the two groups, while the mean concentration of 25-hydroxyvitamin D substantially was lower in case group in comparison with the control group (14.46 VS. 19.88). Furthermore, low levels of vitamin D are associated with DR and consequently proliferative diabetic retinopathy (PDR) in patients with T2DM. CONCLUSION: Totally based on the results of the present study vitamin D deficiency increased the risk of RD in patients with T2DM, also in case of deficiency of this nutrient, retinopathy may develop into PDR type.

Propranolol: a new pharmacologic approach to counter retinopathy of prematurity progression.

Despite the evident progress in neonatal medicine, retinopathy of prematurity (ROP) remains a serious threat to the vision of premature infants, due to a still partial understanding of the mechanisms underlying the development of this disease and the lack of drugs capable of arresting its progression. Although ROP is a multifactorial disease, retinal vascularization is strictly dependent on oxygen concentration. The exposition of the retina of a preterm newborn, still incompletely vascularized, to an atmosphere relatively hyperoxic, as the extrauterine environment, induces the downregulation of proangiogenic factors and therefore the interruption of vascularization (first ischemic phase of ROP). However, over the following weeks, the growing metabolic requirement of this ischemic retina produces a progressive hypoxia that specularly promotes the surge of proangiogenic factors, finally leading to proliferative retinopathy (second proliferative phase of ROP). The demonstration that the noradrenergic system is actively involved in the coupling between hypoxia and the induction of vasculogenesis paved the way for a pharmacologic intervention aimed at counteracting the interaction of noradrenaline with specific receptors and consequently the progression of ROP. A similar trend has been observed in infantile hemangiomas, the most common vascular lesion of childhood induced by pre-existing hypoxia, which shares similar characteristics with ROP. The fact that propranolol, an unselective antagonist of ß1/2 adrenoceptors, counteracts the growth of infantile hemangiomas, suggested the idea of testing the efficacy of propranolol in infants with ROP. From preclinical studies, ongoing clinical trials demonstrated that topical administration of propranolol likely represents the optimal approach to reconcile its efficacy and maximum safety. Given the strict relationship between vessels and neurons, recovering retinal vascularization with propranolol may add further efficacy to prevent retinal dysfunction. In conclusion, the strategy of contrasting precociously the progression of the disease appears to be more advantageous than the current wait-and-see therapeutic approach, which instead is mainly focused on avoiding retinal detachment.

Proliferative Retinopathy in Non-human Immunodeficiency Virus CMV Retinitis.

PURPOSE: To report a case series of human immunodeficiency virus (HIV)-negative patients with healed cytomegalovirus retinitis presenting with proliferative retinopathy (in the form of neovascularisation elsewhere). METHODS: Retrospective case series. Multimodal imaging was performed at each follow-up visit. RESULTS: Three patients with non-HIV immune dysfunction were followed up after healing of CMV retinitis. All three developed neovascularisation. Patient 1 after 4 months presented with vitreous haemorrhage for which pars plana vitrectomy was performed. Patient 2 developed neovascularization at disc and neovascularisation elsewhere 4 months after resolution, and patient 3 despite being affected by bilateral CMV retinitis, presented with unilateral neovascularization at 14 month after resolution of retinitis. CONCLUSION: Increased incidence of this rare entity could be attributed to partial immune dysfunction in non-HIV patients, limited area of retinitis with a more aggressive occlusive vasculitis. Extensive occlusion with more area of viable retina for angiogenic factor production explains this phenomena. It emphasizes the need for continued follow-up even after healing and to differentiate it from reactivation of retinitis and immune recovery uveitis.Abbreviation: CMV: cytomegalovirus; HIV: human immunodeficiency virus; BCVA: best corrected visual acuity.

Triciribine attenuates pathological neovascularization and vascular permeability in a mouse model of proliferative retinopathy.

Proliferative retinopathies are the leading cause of irreversible blindness in all ages, and there is a critical need to identify novel therapies. We investigated the impact of triciribine (TCBN), a tricyclic nucleoside analog and a weak Akt inhibitor, on retinal neurovascular injury, vascular permeability, and inflammation in oxygen-induced retinopathy (OIR). Post-natal day 7 (P7) mouse pups were subjected to OIR, and treated (i.p.) with TCBN or vehicle from P14-P16 and compared with age-matched, normoxic, vehicle or TCBN-treated controls. P17 retinas were processed for flat mounts, immunostaining, Western blotting, and qRT-PCR studies. Fluorescein angiography, electroretinography, and spectral domain optical coherence tomography were performed on days P21, P26, and P30, respectively. TCBN treatment significantly reduced pathological neovascularization, vaso-obliteration, and inflammation marked by reduced TNFα, IL6, MCP-1, Iba1, and F4/80 (macrophage/microglia markers) expression compared to the vehicle-treated OIR mouse retinas. Pathological expression of VEGF (vascular endothelial growth factor), and claudin-5 compromised the blood-retinal barrier integrity in the OIR retinas correlating with increased vascular permeability and neovascular tuft formation, which were blunted by TCBN treatment. Of note, there were no changes in the retinal architecture or retinal cell function in response to TCBN in the normoxia or OIR mice. We conclude that TCBN protects against pathological neovascularization, restores blood-retinal barrier homeostasis, and reduces retinal inflammation without adversely affecting the retinal structure and neuronal function in a mouse model of OIR. Our data suggest that TCBN may provide a novel therapeutic option for proliferative retinopathy.

IL-33 via PKCµ/PRKD1 Mediated α-Catenin Phosphorylation Regulates Endothelial Cell-Barrier Integrity and Ischemia-Induced Vascular Leakage.

Angiogenesis, neovascularization, and vascular remodeling are highly dynamic processes, where endothelial cell-cell adhesion within the vessel wall controls a range of physiological processes, such as growth, integrity, and barrier function. The cadherin-catenin adhesion complex is a key contributor to inner blood-retinal barrier (iBRB) integrity and dynamic cell movements. However, the pre-eminent role of cadherins and their associated catenins in iBRB structure and function is not fully understood. Using a murine model of oxygen-induced retinopathy (OIR) and human retinal microvascular endothelial cells (HRMVECs), we try to understand the significance of IL-33 on retinal endothelial barrier disruption, leading to abnormal angiogenesis and enhanced vascular permeability. Using electric cell-substrate impedance sensing (ECIS) analysis and FITC-dextran permeability assay, we observed that IL-33 at a 20 ng/mL concentration induced endothelial-barrier disruption in HRMVECs. The adherens junction (AJs) proteins play a prominent role in the selective diffusion of molecules from the blood to the retina and in maintaining retinal homeostasis. Therefore, we looked for the involvement of adherens junction proteins in IL-33-mediated endothelial dysfunction. We observed that IL-33 induces α-catenin phosphorylation at serine/threonine (Ser/Thr) residues in HRMVECs. Furthermore, mass-spectroscopy (MS) analysis revealed that IL-33 induces the phosphorylation of α-catenin at Thr654 residue in HRMVECs. We also observed that PKCµ/PRKD1-p38 MAPK signaling regulates IL-33-induced α-catenin phosphorylation and retinal endothelial cell-barrier integrity. Our OIR studies revealed that genetic deletion of IL-33 resulted in reduced vascular leakage in the hypoxic retina. We also observed that the genetic deletion of IL-33 reduced OIR-induced PKCµ/PRKD1-p38 MAPK-α-catenin signaling in the hypoxic retina. Therefore, we conclude that IL-33-induced PKCµ/PRKD1-p38 MAPK-α-catenin signaling plays a significant role in endothelial permeability and iBRB integrity.

Vitreous hemorrhage - Causes, diagnosis, and management.

Vitreous hemorrhage is associated with a myriad of conditions such as proliferative diabetic retinopathy, proliferative retinopathy following vascular occlusion and vasculitis, trauma, retinal breaks, and posterior vitreous detachment without retinal break. Multiple pathological mechanisms are associated with development of vitreous hemorrhage such as disruption of abnormal vessels, normal vessels, and extension of blood from an adjacent source. The diagnosis of vitreous hemorrhage requires a thorough history taking and clinical examination including investigations such as ultra-sonography, which help decide the appropriate time for intervention. The prognosis of vitreous hemorrhage depends on the underlying cause. Treatment options include observation, laser photo-coagulation, cryotherapy, intravitreal injections of anti-vascular endothelial growth factor, and surgery. Pars plana vitrectomy remains the cornerstone of management. Complications of vitreous hemorrhage include glaucoma (ghost cell glaucoma, hemosiderotic glaucoma), proliferative vitreoretinopathy, and hemosiderosis bulbi.

A Study of the Prevalence and Pattern of Sickle Cell Retinopathy among Eye Clinic Attendees in a Nigerian Tertiary Hospital.

Background: Sickle Cell Disease (SCD) is the first and the most common group of haemoglobinopathies in the world. It affects virtually all body systems including the eyes. Proliferative Sickle cell Retinopathy (PSR) is a cause of visual loss in the working age group which has an impact on the economy and quality of life. This study aimed to describe the pattern of presentation of Sickle Cell Retinopathy (SCR)to improve understanding of the disease presentation. Methodology: The ophthalmic surgical records of patients diagnosed with sickle cell disease at the retinal unit, department of Ophthalmology at the Lagos University Teaching Hospital between the year 2011-2020 were reviewed retrospectively. Results: A total of 64 patients (108 eyes) records were reviewed in this study. The Prevalenceof sickle cell retinopathy was 5.4% of all retina cases within the study period. Age ranged from 10-70 years; the mean age was 36.28 years ± 13.66. There were 25 females and 39 males (F:M= 1:1.6). SCR was most common in patients with HbSC 40 (62.5%). Common presenting symptoms were loss of vision34 (53.1%) and floaters 34 (53.1%). Goldberg stage III 26 (20.3%) and stage IV 27 (21.1%) were the most common stages of proliferative disease at presentation. A significant association was seen between Haemoglobin genotype SC and the occurrence of sickle cell retinopathy with 90% of the patients with Haemoglobin genotype SC having had PSR. The majority of the patients25 (39.1%) had no treatment, and 13 (20.3%) had laser photocoagulation only. Conclusion: Sickle cell retinopathy is not uncommon in Nigeria and many patients only present in tertiary health facilities when they have severe symptoms such as loss of vision. This may be attributed to the late diagnosis and referral. Routine screening is recommended to ensure early detection and treatment to prevent avoidable blindness.

THE IMPACT OF TOTAL PHYSICAL ACTIVITY ON MICROVASCULAR COMPLICATIONS IN TYPE 1 DIABETES MELLITUS PATIENTS.

The incidence of diabetes is increasing worldwide, emphasizing an emerging need for blood glucose control optimization to prevent the development of chronic complications and improve the quality of life. This retrospective cohort study aimed to investigate the effects of total physical activity on microvascular diabetic complication development in patients with type 1 diabetes mellitus (T1DM). The study included 71 T1DM patients, average age 41 years and HbA1c 7.78%. Most patients (82.1%) reported having hypoglycemia, while the minority of patients developed microvascular complications, mostly nonproliferative retinopathy (17.7%). All subjects included in the study were moderately or vigorously physically active. No association was observed between total physical activity and regulation of glycemia, hypoglycemic incidents, or development of microvascular complications. Until sufficient data from prospective studies become available, our data support the findings of no negative effect of higher intensity physical activity on the development of microvascular complications in T1DM patients.

Novel therapies for proliferative retinopathies.

Proliferative retinopathies, such as neovascular age-related macular degeneration and proliferative diabetic retinopathy, are a special health issue due to their contribution to irreversible blindness. Although the promoting conditions and physiopathology of proliferative retinopathies are different, these feature a highly detrimental angiogenesis driven by the overproduction of vascular endothelial growth factor (VEGF). This article describes the mechanism of action of ocular antiangiogenic therapies currently found in clinical development. Systems classify accordingly as (a) novel anti-VEGF systems, (b) molecules targeting non-VEGF pathways, and (c) gene therapies. Whereas most therapies are designed to neutralize VEGF, there is a significant set of products with diverse complexity and mechanism of action. Anti-VEGF therapies are still the most studied approach to tackle angiogenesis. Therapies targeting non-VEGF pathways, however, are highlighted because they could be an option for patients nonresponsive to anti-VEGF therapies. Finally, gene therapy is a promissory technology platform but still is subject to demonstrate safety and efficacy.

Proliferative Retinopathy Associated with Repeated High-Altitude Exposure in a Patient with Sickle Cell Trait.

Broadhead Geoffrey K., Henry E. Wiley, David Peprah, Kenneth Olumba, and Alisa T. Thavikulwat. Proliferative retinopathy associated with repeated high-altitude exposure in a patient with sickle cell trait. High Alt Med Biol. 23:369-371, 2022.-Sickle cell trait (SCT), a carrier state characterized by one normal copy of the beta-globin gene (producing hemoglobin A) and one abnormal variant (producing hemoglobin S), is typically asymptomatic and very low risk for manifestations of hemoglobinopathy, including development of retinopathy. Reported cases of proliferative retinopathy in patients with SCT have occurred in the context of concurrent ocular or systemic disease. We report a case of an otherwise healthy patient with SCT who developed proliferative retinopathy requiring surgical intervention in the setting of significant exposure to high altitude through increased work hours as a flight attendant in the month leading to her presentation. Significant high-altitude exposure may contribute to development of retinopathy in patients with sickle trait. Practitioners should consider the possibility of sickle cell retinopathy in patients with sickle trait in these circumstances.

Sphingosine-1-phosphate and ceramide-1-phosphate promote migration, pro-inflammatory and pro-fibrotic responses in retinal pigment epithelium cells.

Retinal pigment epithelium (RPE) cells, essential for preserving retina homeostasis, also contribute to the development of retina proliferative diseases, through their exacerbated migration, epithelial to mesenchymal transition (EMT) and inflammatory response. Uncovering the mechanisms inducing these changes is crucial for designing effective treatments for these pathologies. Sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) are bioactive sphingolipids that promote migration and inflammation in several cell types; we recently established that they stimulate the migration of retina Müller glial cells (Simón et al., 2015; Vera et al., 2021). We here analyzed whether S1P and C1P regulate migration, inflammation and EMT in RPE cells. We cultured two human RPE cell lines, ARPE-19 and D407 cells, and supplemented them with either 5 µM S1P or 10 µM C1P, or their vehicles, for 24 h. Analysis of cell migration by the scratch wound assay showed that S1P addition significantly enhanced migration in both cell lines. Pre-treatment with W146 and BML-241, antagonists for S1P receptor 1 (S1P1) and 3 (S1P3), respectively, blocked exogenous S1P-induced migration. Inhibiting sphingosine kinase 1 (SphK1), the enzyme involved in S1P synthesis, significantly reduced cell migration and exogenous S1P only partially restored it. Addition of C1P markedly stimulated cell migration. Whereas inhibiting C1P synthesis did not affect C1P-induced migration, inhibiting S1P synthesis strikingly decreased it; noteworthy, addition of C1P promoted the transcription of SphK1. These results suggest that S1P and C1P stimulate RPE cell migration and their effect requires S1P endogenous synthesis. Both S1P and C1P increase the transcription of pro-inflammatory cytokines IL-6 and IL-8, and of EMT marker α-smooth muscle actin (α-SMA) in ARPE-19 cells. Collectively, our results suggest new roles for S1P and C1P in the regulation of RPE cell migration and inflammation; since the deregulation of sphingolipid metabolism is involved in several proliferative retinopathies, targeting their metabolism might provide new tools for treating these pathologies.

Authors' response: Proliferative retinopathy in chronic myeloid leukemia and diabetes: A "double whammy".

This editorial discusses that the diabetic proliferative retinopathy progresses as a result of ischemia angiogenic stimuli, which may be exacerbated by concomitant CML retinopathy generating increased blood viscosity and vascular endothelial growth factor levels.

The role of growth hormone and IGF-1 in retinopathy: a prospective study of retinopathy in patients with acromegaly and impaired fasting glucose.

AIMS: To investigate the effects of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis on the incidence and progression of retinopathy. METHODS: We enrolled 91 patients with acromegaly and 123 subjects with impaired fasting glucose (IFG) between 2008 and 2016 to examine the incidence and prevalence of retinopathy. Patients attended follow-ups in our clinics and underwent examinations according to the national guidelines for diabetes management. Both cohorts attended follow-ups until June 2019. RESULTS: Both groups had similar HbA1c, cholesterol, and blood pressure levels. However, patients with acromegaly had higher GH (8.05 ± 16.18 vs. 0.78 ± 1.25 ng/mL) and IGF-1 (547.0 ± 342.1 vs. 146.7 ± 51.4 ng/mL) levels than in subjects with IFG. During the follow-up period, 8 patients (8.8%) with acromegaly and 12 patients (9.8%) with IFG developed some degree of retinopathy. Three patients with acromegaly and two with IFG progressed to proliferative retinopathy. Patients with acromegaly had the same incidence of non-proliferative retinopathy (odds ratio [OR] 0.830; 95% CI 0.318-2.164) and a non-statistically significantly higher incidence of proliferative retinopathy (OR 2.461; 95% CI 0.404-14.988). CONCLUSION: The data reveals that GH and IGF-1 might play a crucial role in the development of proliferative retinopathy and influence its progression. Therefore, we suggest screening patients with acromegaly should be similar to diabetes patients.

Retrolenticular Vitreous Opacities as a Diagnostic Indicator of Systemic Amyloidosis.

Purpose: Systemic amyloidosis is a group of rare, life-threatening disorders characterized by the deposition of amyloid plaques in numerous tissues. Vitreous involvement can occur in amyloidosis and here we describe critical diagnostic findings. Methods: Case report of vitreous amyloidosis diagnosis confounded by non-specific presentation. Results: Despite false-negative vitreous biopsies, in the setting of previous vitreoretinal surgery, the case reveals vitreous opacities, decreased visual acuity, and retinal neovascularization as critical signs in ocular amyloidosis. Conclusions: Here we present the signs and symptoms that raise suspicion for vitreous amyloidosis and how to approach diagnosis early in the disease presentation.

Hypertension: A Cause of Bilateral Proliferative Retinopathy.

Purpose: To describe the case of a 67-year-old female with proliferative retinopathy secondary to uncontrolled hypertension. Methods: Retrospective case report including multimodal imaging. Results: A 67-year-old female presented with mild vitreous hemorrhage, retinal hemorrhage, hard exudate of the left eye and hard exudate, copper wiring of vessels, and retinal hemorrhages in the right eye. Optical coherence tomography depicted macular edema of both eyes. Fluorescein angiography revealed large areas of peripheral retinal ischemia and neovascularization with multiple areas of vascular leakage in both eyes. Conclusions: Proliferative hypertensive retinopathy has been rarely reported in the literature. Our patient exhibited findings consistent with proliferative retinopathy secondary to hypertensive retinopathy.

AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation.

Proliferative retinopathies produces an irreversible type of blindness affecting working age and pediatric population of industrialized countries. Despite the good results of anti-VEGF therapy, intraocular and systemic complications are often associated after its intravitreal use, hence novel therapeutic approaches are needed. The aim of the present study is to test the effect of the AS1411, an antiangiogenic nucleolin-binding aptamer, using in vivo, ex vivo and in vitro models of angiogenesis and propose a mechanistic insight. Our results showed that AS1411 significantly inhibited retinal neovascularization in the oxygen induced retinopathy (OIR) in vivo model, as well as inhibited branch formation in the rat aortic ex vivo assay, and, significantly reduced proliferation, cell migration and tube formation in the HUVEC in vitro model. Importantly, phosphorylated NCL protein was significantly abolished in HUVEC in the presence of AS1411 without affecting NFκB phosphorylation and -21 and 221-angiomiRs, suggesting that the antiangiogenic properties of this molecule are partially mediated by a down regulation in NCL phosphorylation. In sum, this new research further supports the NCL role in the molecular etiology of pathological angiogenesis and identifies AS1411 as a novel anti-angiogenic treatment.

Hypertension as an Unusual Cause of Proliferative Retinopathy: Case Report and Literature Review.

Malignant hypertensive retinopathy is associated with characteristic fundus findings that typically do not include proliferative retinal vascular changes. We present the case of a 34-year-old patient who had bilateral decreased vision and was found to have malignant hypertension with hypertensive retinopathy changes along with unforeseen bilateral neovascularization and vitreous hemorrhage. Detailed history and extensive systemic and ophthalmic workup failed to reveal an alternative explanation for her proliferative retinopathy. Blood pressure control and panretinal photocoagulation halted further deterioration. Malignant hypertensive retinopathy can rarely cause profound retinal ischemia leading to retinal neovascularization. This case further supports the presence of "proliferative hypertensive retinopathy" that needs to be identified and addressed urgently through collaboration between internists and ophthalmologists.