REVIEW OF OPHTHALMIC AND BREASTFEEDING MEDICINE EVIDENCE: Real and Theoretical Risks of Intravitreal Anti-Vascular Endothelial Growth Factor Administration in Lactating Women.

BACKGROUND/PURPOSE: There is limited research regarding the consequences of treating lactating mothers with intravitreal anti-vascular endothelial growth factor (VEGF) agents. Balancing the need for vision-saving treatment, the benefits of breastfeeding, and the concern for affecting the newborn can present a conflict for both mothers and ophthalmologists. This review summarizes the state of the literature regarding the use of intravitreal anti-VEGF agents during breastfeeding along with details about their pharmacology. RESULTS: Bevacizumab and aflibercept have Fc domains subjecting them to FcRn recycling and extending their half-life compared with ranibizumab which is an antibody fragment and lacks the Fc domain. Case reports and small studies have shown that ranibizumab has the lowest serum concentration after intravitreal injection and the least effect on plasma-free VEGF concentrations and breastmilk VEGF levels. CONCLUSION: Clinical and pharmacologic data suggest that ranibizumab has less systemic circulation and effect on maternal serum and breastmilk VEGF levels when compared to bevacizumab and aflibercept. However, there is significant need for further research on the degree and duration to which intravitreal agents circulate systemically, what fraction is transferred into breastmilk and is absorbed, and whether this results in any functional adverse effects to the infant. Other factors to consider in the medical decision-making of lactating mothers necessitating intravitreal anti-VEGF treatment include the gestational and post-natal age of the child and whether it is feasible to avoid breastfeeding for the half-life duration of the intravitreal agent rather than ceasing breastfeeding altogether.

Congenital optic nerve anomaly and migration of subretinal oil: case report and observations in one family.

PURPOSE: To describe a case of optic nerve (ON) anomaly and retinal detachment with extensive subretinal silicone oil after repair of retinal detachment. A three-generation family history of ON anomaly, two generations with detachment, is presented. METHODS: Retrospective chart review. A multigenerational family with ON anomalies and macular detachment. RESULTS: Final repair of retinal detachment was achieved using retinotomy for removal of subretinal 5,000-centistoke silicone oil, gas-fluid exchange, and peripapillary photocoagulation. Silicone oil had been previously used successfully in this eye, yet on subsequent use resulted in subretinal migration. A four patient-three-generation family history of ON anomalies was elicited, and three members were photographed for documentation. CONCLUSION: Optic nerve anomalies and macular detachment present a treatment dilemma because they are associated with poor vision and often a suboptimal visual outcome after surgery. This case demonstrates a large amount of subretinal silicone oil, which migrated over a 2-month period. This case series is a report of a three-generational family demonstrating variable expressivity of ON anomalies complicated by macular detachment in two generations.

A new choroidal mass in a patient with known metastatic leiomyosarcoma: importance of fine-needle aspirate biopsy in diagnostic certainty and treatment planning.

PURPOSE: To report a patient with known metastatic leiomyosarcoma and a new choroidal mass wherein a fine-needle aspirate biopsy was performed to achieve diagnostic and treatment certainty. METHODS: A retrospective case report of one patient. RESULTS: A 63-year-old woman with known metastatic leiomyosarcoma presented with a new choroidal mass. Metastatic leiomyosarcoma to the choroid has been previously reported. An ab externo fine-needle aspirate biopsy was performed to achieve diagnostic and therapeutic certainty (metastatic leiomyosarcoma is considered radiation insensitive and requires local excision, and choroidal melanoma is treated with I135 plaque brachytherapy). The results were positive for choroidal melanoma as read by two different pathologists at two different sites, and the patient was treated in the conventional manner. The response to treatment at 30 months has been excellent. CONCLUSION: When there is diagnostic uncertainty and treatment regimens vary, a fine-needle aspirate biopsy can be diagnostic and can provide direction for care. De novo tumors can be confounded with a metastatic disease in patients with complex histories.

Successful use of anti-VEGF treatment for subretinal hemorrhage and fluid in a young patient with choroidal osteoma.

The authors report the use of an anti-VEGF agent in the resolution of subretinal fluid and hemorrhage with improvement in best corrected visual acuity (BCVA) in a patient with choroidal osteoma. The reported case involves a 20-year-old man who presented with a choroidal osteoma and chronic subretinal fluid associated with hemorrhage. He was treated with six intravitreal doses of bevacizumab over a 13-month period. The fluid resolved and his BCVA improved with these treatments. Intravitreal bevacizumab can be used to successfully treat subretinal fluid associated with choroidal osteomas and may lead to an improvement in BCVA.

Cosmetic facial fillers and severe vision loss.

IMPORTANCE: Dermal injection of cosmetic fillers can lead to irreversible blindness when injected in the forehead, and this possible adverse effect is not typically mentioned to patients. OBSERVATIONS: Vision loss from central retinal artery occlusion occurring, after cosmetic facial enhancement, was irreversible in 3 patients. However, 1 patient had a small amount of recovery with aggressive therapy. CONCLUSIONS AND RELEVANCE: Cosmetic facial fillers are not approved for use in the forehead, but off-label use for enhancement in this region is common. To our knowledge, there have been no prior reports of blindness caused by filler injected into the forehead. We present findings of central retinal artery occlusion due to fillers in 3 patients shortly after their cosmetic procedures. The filler presumably enters the central retinal artery via the rich external-internal carotid anastomoses and becomes embedded in the retinal tissues, potentially leading to irreversible and severe vision loss. Physicians performing cosmetic enhancement procedures involving facial fillers need to be aware of this potential complication and should include significant vision loss as a possible rare complication.

Punctate inner choroidopathy and optic neuropathy: simultaneous presentation in a patient - a case report.

BACKGROUND: We present a case of a patient initially presenting with multifocal choroiditis (MFC) in one eye. She subsequently developed lesions most consistent with punctate inner choroidopathy (PIC) in the contralateral eye, followed by acute vision loss from retrobulbar optic neuropathy. Optic neuropathy has been well described in the setting of MFC. There is, however, only one report of its association with PIC. Punctate inner choroidopathy and MFC have many similarities, with visual loss generally resulting from choroidal neovascularization. In this case, the patient had significant visual loss from presumed retrobulbar optic neuropathy. FINDINGS: The patient responded well to immunomodulation with subsequent return of vision to baseline. CONCLUSIONS: Multifocal choroiditis and punctate inner choroidopathy may be a spectrum of the same disease with many overlapping presentations, including optic neuropathy. Good visual recovery and remission were attained with mycophenolate mofetil and systemic corticosteroid treatment.

The establishment of a predictive mutational model of the forkhead domain through the analyses of FOXC2 missense mutations identified in patients with hereditary lymphedema with distichiasis.

The FOX family of transcription factor genes is an evolutionary conserved, yet functionally diverse class of transcription factors that are important for regulation of energy homeostasis, development and oncogenesis. The proteins encoded by FOX genes are characterized by a conserved DNA-binding domain known as the forkhead domain (FHD). To date, disease-causing mutations have been identified in eight human FOX genes. Many of these mutations result in single amino acid substitutions in the FHD. We analyzed the molecular consequences of two disease-causing missense mutations (R121H and S125L) occurring in the FHD of the FOXC2 gene that were identified in patients with hereditary lymphedema with distichiasis (LD) to test the predictive capacity of a FHD structure/function model. On the basis of the FOXC2 solution structure, both FOXC2 missense mutations are located on the DNA-recognition helix of the FHD. A mutation model based on the parologous FOXC1 protein predicts that these FOXC2 missense mutations will impair the DNA-binding and transcriptional activation ability of the FOXC2 protein. When these mutations were analyzed biochemically, we found that both mutations did indeed reduce the DNA binding and transcriptional capacity. In addition, the R121H mutation affected nuclear localization of FOXC2. Together, these data indicate that these FOXC2 missense mutations are functional nulls and that FOXC2 haploinsufficiency underlies hereditary LD and validates the predictive ability of the FOXC1-based FHD mutational model.

Potentiating the benefit of vascular-supplied glutamine during small bowel storage: importance of buffering agent.

BACKGROUND: Glutamine (gln)-supplemented University of Wisconsin (UW) solution improves overall small bowel (SB) preservation. Sustained gln metabolism in a system devoid of hepatic detoxification will necessarily result in the accumulation of pH active end products leading to nonphysiologic pH shifts. We hypothesized that simultaneous addition of N,N-bis[2-hydroxyethyl]-2-aminoethane sulfonic acid (BES), a known buffering agent, would potentiate the beneficial effect of gln supplementation by addressing the fundamental metabolic principle of pH homeostasis. METHODS: Sprague-Dawley SB rats were administered a vascular flush with one of four solutions: UW; UW+90 mM BES (UWB); UW+2% gln (UWG); or UW+2% gln+90 mM BES (UWBG). Indices of energetics, barrier function, gln catabolism, and histology (light and electron microscopy) were assessed over a 10-hr cold storage time course. RESULTS: Superior gln utilization in the UWBG group was indicated by elevated levels of key catabolites (glutamate, aspartate, glycine, ammonia). The addition of BES and gln resulted in significantly higher levels of all energetic parameters (ATP, total adenylates) at 10 hr compared with UW, UWB, and/or UWG. Barrier function was markedly improved after 10 hr storage in the UWBG group; mannitol permeability was 169 nmol/cm2/hr versus 572 and 445 nmol/cm(2)/hr (for UW and UWG, respectively). Histologic injury at 10 hr was 5.5, 7.5, and 8 (Park's grade) for UWBG, UWG, and UW. Ultrastructural damage was markedly reduced with UWBG, as assessed by grade of mitochondria damage. CONCLUSION: This study strongly supports that the beneficial effects of gln-enriched UW solution can be amplified when combined with an effective buffering agent such as BES.