Akshay Gopinathan Nair
Akshay Gopinathan Nair received his medical degree from Maharashtra University of Health Sciences, India, and completed his residency training in ophthalmology from Sankara Nethralaya in Chennai, India. Following this, he underwent fellowship training in ophthalmic plastic surgery, ocular oncology, and facial aesthetics at L V Prasad Eye Institute, Hyderabad, India, and New York Eye & Ear Infirmary of Mount Sinai, USA. Dr. Nair has over 50 peer-reviewed publications and 8 book chapters in ophthalmology. His areas of special interest are ocular surface and eyelid tumors, ophthalmic imaging, and neuroimaging. Dr. Nair is a faculty member at Lokmanya Tilak Municipal Medical College, Mumbai, India, and is also affiliated with Advanced Eye Hospital & Institute and Aditya Jyot Eye Hospital in Mumbai.
Milind N. Naik
Dr. Milind Naik acquired his postgraduate training in Ophthalmology at the Christian Medical College, Vellore, India. He further completed his ophthalmic and facial plastic surgery fellowship at the prestigious University of California, Los Angeles, in the year 2006–2007. His areas of interest include aesthetic and facial plastic surgery, thyroid eye disease, and minimally invasive ophthalmic plastic surgery.
Dr. Naik has been awarded the Senior Achievement Award by the American Academy of Ophthalmology in the year 2015, and has served as the Vice President of the Asia Pacific Society of Ophthalmic Plastic and Reconstructive Surgery in the year 2010–2012.
Dr. Naik has over 100 peer-reviewed publications in international journals and lectures extensively across the globe in the field of ophthalmic plastic surgery and facial aesthetics. He currently heads the Ophthalmic Plastic Surgery Services at LV Prasad Eye Institute, Hyderabad, India. He also serves as Adjunct Associate Professor, Department of Ophthalmology and Visual Sciences, University of Rochester, New York, USA.
Dr. Naik’s extracurricular interests include painting, 3D videography, and paperfolding.
Dr. Naik’s better half, Dr. Vibhavari Naik is an anesthesiologist, and they have a 16-year-old daughter, Jaee.
Most ophthalmologists routinely treat clinical conditions that seldom have ramifications beyond the eye. An ophthalmologist commonly may come across conditions that may present as immediate threats to the visual system and can lead to permanent loss of visual function if left untreated. Such vision-threatening emergencies such as orbital hemorrhage, central retinal artery occlusion, and chemical burns require prompt action to salvage vision. However, it is uncommon for the ophthalmologist to come across emergencies, which if not treated immediately have the potential to become life-threatening conditions. The oculoplastic surgeon is the one who usually sees such conditions, and therefore it is important to know how to diagnose and treat these life-threatening infective emergencies in oculoplastic practice. In this chapter, cavernous sinus thrombosis, periocular necrotizing fasciitis, and invasive fungal sinusitis will be discussed in detail.
Cavernous Sinus Thrombosis
Cavernous sinus thrombosis (CST) is defined as thrombophlebitis of the cavernous sinus. CST is a dramatic and potentially fatal condition which is seen commonly in children and young adults . CST usually is seen as an indicator of an infectious process which is fast evolving and spreading, most commonly craniofacial in origin . However, with the advent of broad-spectrum antibiotics, CST is not commonly encountered off late. Late recognition and delay in treatment can increase the risk of morbidity and mortality.
The venous drainage of the brain is a part of a unique system where all the dural sinuses, which are interconnected in a complex network, finally drain into the internal jugular vein . The cavernous sinuses receive blood from the ophthalmic veins, the superficial middle and inferior cerebral veins, and the sphenoparietal and sphenoid sinuses. From the cavernous sinuses, the blood drains into the pterygoid plexus via emissary veins and also into the internal jugular vein via the inferior petrosal sinus and the sigmoid sinus through the superior sinus . There are no directional valves in the cavernous sinus and its connections, therefore allowing bidirectional spread of infection and also leading to extensive thrombi throughout the network of sinuses .
Common facial infections that may potentially lead to CST include sinusitis, especially those that originate from the sphenoid, ethmoid, and frontal sinuses, superficial infections that arise from the middle one third of the face. Orbital cellulitis, dental abscesses, septic foci in the nose, tonsils, soft palate, and ears may constitute primary source of the infection that leads to CST.
The most common feature is headache, and it usually precedes fever and the cranial neuropathies. The classical clinical features seen include decrease or loss of vision, chemosis, proptosis, and paralysis of the cranial nerves that course through the cavernous sinus. Ptosis and mydriasis resulting from III nerve dysfunction may also be seen as the disease progresses .
In most cases, CST is usually a clinical diagnosis. Radiologically, MRI and MR venography are more sensitive compared to CT scans for diagnosis. Typically it may show a heterogeneous signal from the abnormal cavernous sinus along with deformity of the cavernous portion of the internal carotid artery and a hyperintense signal of thrombosed vascular sinuses . Other features that may also be seen are dilated superior ophthalmic vein and proptosis on the ipsilateral side. Gallium scintigraphy has occasionally been used as a confirmatory tool in septic CST, demonstrating increased uptake in the cavernous sinus .
Immediate institution of broad-spectrum antibiotics that give coverage against gram-positive, gram-negative, and anaerobic bacteria is essential. Surgical management of the primary septic focus is recommended to reduce the bacterial load in cases such as nasal infections, necrotizing fasciitis. Empirical antimicrobial therapy usually depends on the antecedent clinical condition and must include coverage for methicillin-resistant Staphylococcus aureus (MRSA). An empirical combination, consisting of parenteral metronidazole, vancomycin, and ceftriaxone, will achieve reasonable CSF and brain penetration and will be active against S. aureus . Microbiological testing to narrow down the spectrum and isolate the offending pathogen will help to choose the right antimicrobial agent. Once antibiotics show effect, authors have also reported beneficial use of intravenous steroids in reducing edema .
The role of anticoagulants is still controversial. There have been no controlled trials; however, it is reported that early institution (within 5–7 days) may help in reducing morbidity, but delayed use provides no benefits [2, 9]. The rationale behind anticoagulant therapy is to prevent thrombus propagation, recanalize occluded sinuses and cerebral veins, and prevent complications of deep vein thrombosis and pulmonary embolism . This however has to weigh against the risk of an intracranial bleed and also tendency for sinus infarcts to become hemorrhagic even before anticoagulants have been administered .
Rare but potential complications include carotid thrombosis, brain abscess, and meningitis. However, with prompt treatment, the prognosis of septic CST has improved reducing mortality from near 100 % to 20–30 % . Residual sequelae such as numbness, paresthesia, ptosis, and residual squint have been noted.
Cavernous sinus thrombosis is a rare but potentially fatal, rapidly progressive condition that requires a high clinical suspicion, immediate institution of intensive treatment primarily consisting of broad-spectrum antibiotics along with appropriate surgical drainage of the source of infection, anticoagulants, and possibly steroids.
Periorbital Necrotizing Fasciitis
Necrotizing fasciitis (NF) is an infection of the subcutaneous tissue and superficial fascia accompanied with secondary necrosis of the skin. Although the periorbital tissue is not a common site, when affected, it is associated with a mortality rate ranging from 8 to 15 % and 13.8 % of the patients have resultant loss of vision . Periorbital necrotizing fasciitis (PNF) is one of the few rare situations where an ophthalmologist deals with a potentially life-threatening entity.
PNF most commonly has a history of preceding trauma. In many cases, the trauma is extremely trivial and the patient may not be able to recollect it. In an exhaustive review of available literature on PNF, Amrith et al. reported that in as many as 35 % cases, trauma was identified as the main triggering factor . Recent surgery, immunosuppression, and chemotherapy were also noted; however in a substantial proportion of cases (27 %), no triggering factor was found . Preexisting comorbidities that were noted in this review included alcoholism, diabetes mellitus, and collagen vascular diseases such as rheumatoid arthritis, systemic lupus, deep vein thrombosis, and cardiovascular diseases [14, 15].
Based on the microbiological profile, necrotizing fasciitis is broadly divided into two types. Type 1 NF is polymicrobial and caused by both aerobic and anaerobic organisms. A single organism, such as Streptococcus or Staphylococcus, or a combination of the two, causes type 2 NF. Type 1 NF is commonly seen in patients with immunocompromised status, as compared to patients with type 2 NF (more commonly seen in the periorbital area) often have no such immunodeficiency [13, 16]. The most commonly reported offending organism is gram-positive group A β-hemolytic Streptococcus (GABHS) closely followed by Pseudomonas species.
Clinical Picture and Pathophysiology
PNF usually begins as an acutely presenting painful nonspecific erythematous rash with edema resembling preseptal cellulitis. The infection slowly progresses and the patient may complain a deep periorbital pain . The vascular orbicularis muscle acts as a barrier between the superficial skin and the periorbita below. If untreated, it soon gains entry into the superficial and deep fascial planes, and the infection spreads rapidly . The thin skin of the eyelids however allows clinical signs to be easily detectable early on in the course of the disease . The dermis is attached firmly at the nasojugal fold medially and the malar fold laterally which is a firm attachment and prevents the spread of infection. However once the infection is able to overcome this anatomical hurdle, it quickly spreads following the path of least resistance across the nasal bridge and also into the deep fascial planes of the neck and face, probably accounting for the high number of bilateral cases . It is extremely important to differentiate NF from orbital cellulitis as the clinical picture in both, eye pain, periorbital swelling, and/or fever, may be similar. This is mainly because in PNF, a far more aggressive approach that includes parenteral antibiotics and surgical debridement is necessary .
Systemically, a low- to medium-grade fever associated with tachycardia out of proportion to the temperature elevation is seen . Over the next 48 h, a violaceous discoloration is noted along with bullae over the skin. As the disease progresses, the bacterial toxins released by the pathogens are responsible for angiothrombotic microbial invasion and liquefactive necrosis . As the infection progresses deeper, the fascia are infiltrated by leukocytes, with thrombosis of nutrient vessels and occasional suppuration of the veins and arteries that pass through the fascia, causing black or avascular necrotic patches (Fig. 35.1) . Subsequently the bacteria then proliferate within the destroyed fascia. Eventually, cutaneous gangrene develops within 96 h of the infection setting in. The skin sloughs to become gangrenous due to underlying suppuration by day 10 .
A young male with right periorbital necrotizing fasciitis following trauma to the upper eyelid. Note the white, avascular eschar and the surrounding cellulitis that rapidly spread within the subfascial planes
Radiological investigations such as CT and MRI may help in identifying the extent of the infection as well as the depth of the infection. CT, however, remains as the investigation of choice since it offers easy localization of the initial site of infection, extent of disease, presence of fluid-filled bullae and gas, and anatomical information which may help to guide surgical exploration . That aside, the diagnosis of PNF is primarily clinical, and the treatment must not be delayed for the sake of investigations .
The differentials that may be considered include blepharitis, conjunctivitis, preseptal cellulitis, orbital cellulitis, endophthalmitis, cavernous sinus thrombosis, and rhino-orbital mucormycosis [13, 15, 16]. The absence of the violaceous hue, bullae, crepitus, and subsequent necrosis can help to differentiate orbital cellulitis from PNF.
Early recognition, prompt diagnosis, aggressive medical therapy, and surgical debridement can help prevent fatal outcomes in PNF. The treatment largely rests on the institution of broad-spectrum antibiotics and surgical debridement. Hyperbaric oxygen has been shown to play a beneficial role in the treatment of NF. Empirical antimicrobial therapy should consist of beta-lactam antibiotics, such as penicillin or cephalosporin and clindamycin . The selected broad-spectrum antibiotics should be effective against β-hemolytic Streptococcus .
However, once the diagnosis is established, regardless of whether antibiotics have been initiated, prompt and adequate operative debridement should be carried out at this time, whether necrotic tissue is already present or not . Gradually as the antibiotics are administered, a clear zone of demarcation will appear over the next few hours which will permit further debridement to be done either at the bedside or in the operating room. The surgical exploration and debridement must ensure that all the necrotic tissue is completely excised. The aim of debridement is to remove all nonviable tissue; this reduced the bacterial load and the level of circulating toxins as well as halted the progression of infection. It may also be prudent to perform an exploratory incision over an area beyond the limits of debridement when it is uncertain whether necrosis is undermining viable skin [16, 18, 19].
It has been noted that in PNF, preserving viable skin and orbicularis oculi muscle promotes the action of antibiotics, which thus improves healing, preventing, or reducing morbidity and facial disfigurements . Hyperbaric oxygen therapy has been shown to reduce mortality, but it has also been shown to improve the salvage of tissue viability . Hyperbaric oxygen therapy leads to inhibition of exotoxin production, improved leukocyte function, attainment of sufficient tissue oxygen levels which kills strict anaerobes, and inhibition of growth of facultative anaerobes .
The possible sequelae of PNF that often causes vision loss are central retinal artery occlusion, orbital spread necessitating removal of orbital contents including eyeball [19, 27], or corneal perforation . Lagophthalmos that leads to exposure keratopathy can also be one of the causes of vision loss. Reconstruction can only begin once the infection is resolved and the wound is clean and stable .
The most critical factors for reducing mortality from NF remain early recognition and urgent operative debridement [29, 30]. NF involving the lower part of the face and cervical area (30 %) than that involving the upper and the middle areas of the face (10–12.5 %)  – primarily due to contiguous spread into important structures such as the mediastinum, chest, and carotid sheath – results in pulmonary complications and death. Other causes for mortality include systemic complications like septicemia, shock, and multi-organ failure . The delay between hospital admission and initial debridement and broad-spectrum antibiotic therapy initiation should be considered as the most critical factor influencing morbidity and mortality .
In summary, the key to good outcomes in PNF lies in early diagnosis and institution of treatment. Multiple surgical debridement, if necessary, prevents escalation to toxic shock, which seems to precede all deaths reported in literature.
Invasive Fungal Sinusitis
One more addition to the list of diseases presenting to the ophthalmologist that are potentially curable if identified and treated early, but fatal if detected late, is fungal sinusitis. Fungal sinusitis has two basic clinical forms: invasive and noninvasive. Based on the tempo of evolution, invasive fungal sinusitis can be classified as acute, subacute, or chronic [31–33].
Fungal sinusitis is known to occur when common saprophytes of the paranasal sinuses invade the paranasal sinus mucosa, frequently in the setting of an immunocompromised state [31, 34]. The invasive fungal sinusitis (IFS) gradually proceeds to extend from the paranasal sinuses into the orbit and then on to the orbital apex, from where it further spreads into the cavernous sinus and cavernous carotid artery, causing carotid occlusion, cerebral infarction, intracranial aneurysms and hemorrhage, meningitis, cerebral abscess, and eventually leading up to the inevitable consequence of this entity – death .